2021
|
Tasta, Oriane; Swiader, Audrey; Grazide, Marie-Hélène; Rouahi, Myriam; Parant, Olivier; Vayssière, Christophe; Bujold, Emmanuel; Salvayre, Robert; Guerby, Paul; Negre-Salvayre, Anne A role for 4-hydroxynonenal in premature placental senescence in Preeclampsia and Intrauterine Growth Restriction Journal Article In: Free Radical Biology & Medicine, 2021, ISSN: 1873-4596. @article{tasta_role_2021,
title = {A role for 4-hydroxynonenal in premature placental senescence in Preeclampsia and Intrauterine Growth Restriction},
author = {Tasta, Oriane and Swiader, Audrey and Grazide, Marie-Hélène and Rouahi, Myriam and Parant, Olivier and Vayssière, Christophe and Bujold, Emmanuel and Salvayre, Robert and Guerby, Paul and Negre-Salvayre, Anne},
doi = {10.1016/j.freeradbiomed.2021.01.002},
issn = {1873-4596},
year = {2021},
date = {2021-01-01},
journal = {Free Radical Biology & Medicine},
abstract = {Premature placental senescence is a hallmark of pregnancy-related disorders such as intrauterine growth restriction (IUGR) and preeclampsia (PE), two major cause of maternal and neonatal morbidity and mortality. Oxidative stress and lipid peroxidation are involved in the pathogenesis of PE and IUGR, and may play a role in placental aging. In this study, we investigated whether 4-hydroxy-2-nonenal (HNE), a lipid peroxidation-derived aldehyde present in preeclamptic placentas, may contribute to premature senescence in placenta-related complications. Placentas from PE-affected women, exhibited several senescence patterns, such as an increased expression of phosphorylated (serine-139) histone γ-H2AX, a sensitive marker of double-stranded DNA breaks, the presence of lipofuscin granules, and an accumulation of high molecular weight cross-linked and ubiquitinated proteins. PE placentas showed an accumulation of acetylated proteins consistent with the presence of HNE-adducts on sirtuin 1 (SIRT1). Likewise, oxidative stress and senescence markers together with SIRT1 modification by HNE, were observed in murine placentas from mice treated with lipopolysaccharide during gestation and used as models of IUGR. The addition of HNE and ONE (4-oxo-2-nonenal), to cultured HTR-8/SVneo human trophoblasts activated the senescence-activated β-galactosidase, and generated an accumulation of acetylated proteins, consistent with a modification of SIRT1 by HNE. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in premature placental senescence in PE and IUGR, and more generally in pathological pregnancies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Premature placental senescence is a hallmark of pregnancy-related disorders such as intrauterine growth restriction (IUGR) and preeclampsia (PE), two major cause of maternal and neonatal morbidity and mortality. Oxidative stress and lipid peroxidation are involved in the pathogenesis of PE and IUGR, and may play a role in placental aging. In this study, we investigated whether 4-hydroxy-2-nonenal (HNE), a lipid peroxidation-derived aldehyde present in preeclamptic placentas, may contribute to premature senescence in placenta-related complications. Placentas from PE-affected women, exhibited several senescence patterns, such as an increased expression of phosphorylated (serine-139) histone γ-H2AX, a sensitive marker of double-stranded DNA breaks, the presence of lipofuscin granules, and an accumulation of high molecular weight cross-linked and ubiquitinated proteins. PE placentas showed an accumulation of acetylated proteins consistent with the presence of HNE-adducts on sirtuin 1 (SIRT1). Likewise, oxidative stress and senescence markers together with SIRT1 modification by HNE, were observed in murine placentas from mice treated with lipopolysaccharide during gestation and used as models of IUGR. The addition of HNE and ONE (4-oxo-2-nonenal), to cultured HTR-8/SVneo human trophoblasts activated the senescence-activated β-galactosidase, and generated an accumulation of acetylated proteins, consistent with a modification of SIRT1 by HNE. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in premature placental senescence in PE and IUGR, and more generally in pathological pregnancies. |
Vidal, Fabien; Guerby, Paul; Simon, Cynthia; Lesourd, Florence; Cartron, Géraldine; Parinaud, Jean; Tanguy le Gac, Yann; Dupuis, Ninon Spontaneous pregnancy rate following surgery for deep infiltrating endometriosis in infertile women: The impact of the learning curve Journal Article In: Journal of Gynecology Obstetrics and Human Reproduction, vol. 50, no. 1, pp. 101942, 2021, ISSN: 2468-7847. @article{vidal_spontaneous_2021,
title = {Spontaneous pregnancy rate following surgery for deep infiltrating endometriosis in infertile women: The impact of the learning curve},
author = {Vidal, Fabien and Guerby, Paul and Simon, Cynthia and Lesourd, Florence and Cartron, Géraldine and Parinaud, Jean and Tanguy le Gac, Yann and Dupuis, Ninon},
doi = {10.1016/j.jogoh.2020.101942},
issn = {2468-7847},
year = {2021},
date = {2021-01-01},
journal = {Journal of Gynecology Obstetrics and Human Reproduction},
volume = {50},
number = {1},
pages = {101942},
abstract = {OBJECTIVES: To determine whether the surgical learning curve impact the spontaneous pregnancy rate in infertile patients undergoing removal of deep infiltrating endometriosis MATERIAL AND METHODS: Single center retrospective study including the first 50 consecutive infertile women suffering from deep infiltrating endometriosis and referred to a single surgeon. All patients underwent laparoscopic removal of deep endometriosis lesions. The study population was stratified in two subgroups, namely the early group (including the first 25 cases) and the late group (comprising the 25 subsequent cases). Pregnancy and live birth rates, surgical morbidity and clinical recurrence rate were compared between study groups. RESULTS: Overall, spontaneous pregnancy rate (40 % in the early group versus 56 % in the late group},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: To determine whether the surgical learning curve impact the spontaneous pregnancy rate in infertile patients undergoing removal of deep infiltrating endometriosis MATERIAL AND METHODS: Single center retrospective study including the first 50 consecutive infertile women suffering from deep infiltrating endometriosis and referred to a single surgeon. All patients underwent laparoscopic removal of deep endometriosis lesions. The study population was stratified in two subgroups, namely the early group (including the first 25 cases) and the late group (comprising the 25 subsequent cases). Pregnancy and live birth rates, surgical morbidity and clinical recurrence rate were compared between study groups. RESULTS: Overall, spontaneous pregnancy rate (40 % in the early group versus 56 % in the late group |
Boutin, Amélie; Gasse, Cédric; Guerby, Paul; Giguère, Yves; Tétu, Amélie; Bujold, Emmanuel First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study Journal Article In: Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC, vol. 43, no. 1, pp. 43–49, 2021, ISSN: 1701-2163. @article{boutin_first-trimester_2021,
title = {First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study},
author = {Boutin, Amélie and Gasse, Cédric and Guerby, Paul and Giguère, Yves and Tétu, Amélie and Bujold, Emmanuel},
doi = {10.1016/j.jogc.2020.06.011},
issn = {1701-2163},
year = {2021},
date = {2021-01-01},
journal = {Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC},
volume = {43},
number = {1},
pages = {43--49},
abstract = {OBJECTIVES: To estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women.
METHODS: We conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth.
RESULTS: Among 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75-0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%-73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%-37%).
CONCLUSIONS: The combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVES: To estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women.
METHODS: We conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth.
RESULTS: Among 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75-0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%-73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%-37%).
CONCLUSIONS: The combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes. |
2020
|
Fillion, Alexandre; Guerby, Paul; Menzies, Didier; Lachance, Caroline; Comeau, Marie-Pier; Bussières, Marie-Claude; Doucet-Gingras, Félicia-Allysson; Zérounian, Sophie; Bujold, Emmanuel Pathological investigation of placentas in preeclampsia (the PEARL study) Journal Article In: Hypertension in Pregnancy, pp. 1–7, 2020, ISSN: 1525-6065. @article{fillion_pathological_2020,
title = {Pathological investigation of placentas in preeclampsia (the PEARL study)},
author = {Fillion, Alexandre and Guerby, Paul and Menzies, Didier and Lachance, Caroline and Comeau, Marie-Pier and Bussières, Marie-Claude and Doucet-Gingras, Félicia-Allysson and Zérounian, Sophie and Bujold, Emmanuel},
doi = {10.1080/10641955.2020.1866008},
issn = {1525-6065},
year = {2020},
date = {2020-12-01},
journal = {Hypertension in Pregnancy},
pages = {1--7},
abstract = {INTRODUCTION: Preeclampsia (PE), but mainly preterm PE, is associated with deep placentation disorders. We aimed to compare placental pathologies in pregnancies affected by term and preterm PE compared to normal pregnancies. METHODS: We performed a prospective case-cohort study. Low-risk nulliparous women were recruited in the first trimester and women who developed PE were recruited at diagnosis. Placental pathologies were reported according to the Amsterdam Placental Workshop Group Consensus Statement and were compared between cases and controls. PE cases stratified as term (≥37 weeks) and preterm PE (textless37 weeks). Our primary outcome was maternal vascular malperfusion (MVM). RESULTS: Twenty-four women who developed preterm PE were compared to 10 women who developed term PE and 41 women without PE. Preterm PE (92%) was associated with more MVM than term PE (10%, p textless 0.01) and controls (4%, p textless 0.01), but the rate of MVM was similar between term PE and controls (p = 0.56). Preterm PE was also associated with more placental infarcts (65% vs. 20% vs. 15%); advanced villous maturation (91% vs. 30% vs. 1%); and hypoplastic villous maturation (70% vs. 10% vs. 3%); and moderate to severe decidual vasculopathy (56% vs. 10% vs. 3%) than term PE and controls (all p textless 0.05). CONCLUSION: Most cases of preterm PE are associated with MVM, placental infarcts, advanced and/or hypoplastic villous maturation, and moderate to severe decidual vasculopathy, while it is infrequent in term PE and pregnancies without PE. Preterm and term preeclampsia have a different pathologic process that should be considered for their prevention and clinical management.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Preeclampsia (PE), but mainly preterm PE, is associated with deep placentation disorders. We aimed to compare placental pathologies in pregnancies affected by term and preterm PE compared to normal pregnancies. METHODS: We performed a prospective case-cohort study. Low-risk nulliparous women were recruited in the first trimester and women who developed PE were recruited at diagnosis. Placental pathologies were reported according to the Amsterdam Placental Workshop Group Consensus Statement and were compared between cases and controls. PE cases stratified as term (≥37 weeks) and preterm PE (textless37 weeks). Our primary outcome was maternal vascular malperfusion (MVM). RESULTS: Twenty-four women who developed preterm PE were compared to 10 women who developed term PE and 41 women without PE. Preterm PE (92%) was associated with more MVM than term PE (10%, p textless 0.01) and controls (4%, p textless 0.01), but the rate of MVM was similar between term PE and controls (p = 0.56). Preterm PE was also associated with more placental infarcts (65% vs. 20% vs. 15%); advanced villous maturation (91% vs. 30% vs. 1%); and hypoplastic villous maturation (70% vs. 10% vs. 3%); and moderate to severe decidual vasculopathy (56% vs. 10% vs. 3%) than term PE and controls (all p textless 0.05). CONCLUSION: Most cases of preterm PE are associated with MVM, placental infarcts, advanced and/or hypoplastic villous maturation, and moderate to severe decidual vasculopathy, while it is infrequent in term PE and pregnancies without PE. Preterm and term preeclampsia have a different pathologic process that should be considered for their prevention and clinical management. |
Tapp, Sylvie; Guerby, Paul; Girard, Mario; Roberge, Stéphanie; Côté, Stéphane; Ferreira, Ema; Leclair, Grégoire; Bujold, Emmanuel A Pilot Randomized Trial Comparing the Effects of 80 versus 160 mg of Aspirin on Midtrimester Uterine Artery Pulsatility Index in Women with a History of Preeclampsia Journal Article In: Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC, vol. 42, no. 12, pp. 1498–1504, 2020, ISSN: 1701-2163. @article{tapp_pilot_2020,
title = {A Pilot Randomized Trial Comparing the Effects of 80 versus 160 mg of Aspirin on Midtrimester Uterine Artery Pulsatility Index in Women with a History of Preeclampsia},
author = {Tapp, Sylvie and Guerby, Paul and Girard, Mario and Roberge, Stéphanie and Côté, Stéphane and Ferreira, Ema and Leclair, Grégoire and Bujold, Emmanuel},
doi = {10.1016/j.jogc.2020.05.013},
issn = {1701-2163},
year = {2020},
date = {2020-12-01},
journal = {Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC},
volume = {42},
number = {12},
pages = {1498--1504},
abstract = {OBJECTIVE: To compare the effects of 80 mg and 160 mg of aspirin, initiated in the first trimester of pregnancy, on mid-trimester uterine artery pulsatility index (UtA-PI) in women with a history of preeclampsia.
METHODS: We performed a pilot double-blind randomized controlled trial. Pregnant women with a history of preeclampsia were recruited between 100/7 and 136/7 weeks gestation and randomly assigned to take either 80 or 160 mg of aspirin daily at bedtime from randomization to 356/7 weeks gestation. The primary outcome was mean UtA-PI at 22-24 weeks. Secondary outcomes included the rate of fetal growth restriction and preeclampsia, stratified as term (≥37 weeks), preterm (textless37 weeks), and early-onset (textless34 weeks) preeclampsia. RESULTS: A total of 107 participants were randomized, including 41 (38%) with a history of preterm preeclampsia and 16 (15%) with a history of early-onset preeclampsia. We observed no significant difference in mean UtA-PI at 22-24 weeks between the 2 groups (0.97; 95% CI 0.88-1.05 vs. 0.97; 95% CI 0.88-1.07, P = 0.9). The rates of fetal growth restriction (8% vs. 2%; P = 0.20); preeclampsia (12% vs. 15%; P = 0.78), preterm preeclampsia (4% vs. 2%; P = 0.56), and early-onset preeclampsia (0% vs. 2%; P = 0.52) were similar in both groups. No serious adverse events associated with the study treatment were reported.
CONCLUSION: We observed no significant difference in UtA-PI between the two doses of aspirin, but we observed low rates of fetal growth restriction and preterm and early-onset preeclampsia (all less than 5%). The benefits of aspirin for the prevention of preterm preeclampsia is probably not related to the improvement of deep placentation alone.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To compare the effects of 80 mg and 160 mg of aspirin, initiated in the first trimester of pregnancy, on mid-trimester uterine artery pulsatility index (UtA-PI) in women with a history of preeclampsia.
METHODS: We performed a pilot double-blind randomized controlled trial. Pregnant women with a history of preeclampsia were recruited between 100/7 and 136/7 weeks gestation and randomly assigned to take either 80 or 160 mg of aspirin daily at bedtime from randomization to 356/7 weeks gestation. The primary outcome was mean UtA-PI at 22-24 weeks. Secondary outcomes included the rate of fetal growth restriction and preeclampsia, stratified as term (≥37 weeks), preterm (textless37 weeks), and early-onset (textless34 weeks) preeclampsia. RESULTS: A total of 107 participants were randomized, including 41 (38%) with a history of preterm preeclampsia and 16 (15%) with a history of early-onset preeclampsia. We observed no significant difference in mean UtA-PI at 22-24 weeks between the 2 groups (0.97; 95% CI 0.88-1.05 vs. 0.97; 95% CI 0.88-1.07, P = 0.9). The rates of fetal growth restriction (8% vs. 2%; P = 0.20); preeclampsia (12% vs. 15%; P = 0.78), preterm preeclampsia (4% vs. 2%; P = 0.56), and early-onset preeclampsia (0% vs. 2%; P = 0.52) were similar in both groups. No serious adverse events associated with the study treatment were reported.
CONCLUSION: We observed no significant difference in UtA-PI between the two doses of aspirin, but we observed low rates of fetal growth restriction and preterm and early-onset preeclampsia (all less than 5%). The benefits of aspirin for the prevention of preterm preeclampsia is probably not related to the improvement of deep placentation alone. |
Guerby, Paul; Fillion, Alexandre; O'Connor, Sarah; Bujold, Emmanuel Heparin for preventing adverse obstetrical outcomes in pregnant women with antiphospholipid syndrome, a systematic review and meta-analysis Journal Article In: Journal of Gynecology Obstetrics and Human Reproduction, pp. 101974, 2020, ISSN: 2468-7847. @article{guerby_heparin_2020,
title = {Heparin for preventing adverse obstetrical outcomes in pregnant women with antiphospholipid syndrome, a systematic review and meta-analysis},
author = {Guerby, Paul and Fillion, Alexandre and O'Connor, Sarah and Bujold, Emmanuel},
doi = {10.1016/j.jogoh.2020.101974},
issn = {2468-7847},
year = {2020},
date = {2020-11-01},
journal = {Journal of Gynecology Obstetrics and Human Reproduction},
pages = {101974},
abstract = {BACKGROUND: We performed a systematic review and meta-analysis to assess the efficacy and safety of heparin for preventing adverse obstetrical outcomes in pregnant women with antiphospholipid syndrome (APS).
METHODS: We reviewed randomized controlled trials from CENTRAL, EMBASE, MEDLINE, and Web of science (inception to November 5th 2019), and relevant article reference lists. Two reviewers independently screened and extracted data from trials investigating heparin, including Low Molecular Weight Heparin (LMWH) and unfractionated heparin (UFH) at any dose, associated or not with aspirin, compared to any comparator group in pregnant women with APS. Internal validity was assessed in duplicate using the Cochrane Risk of Bias tool. The strength of evidence was assessed in duplicate using the Grading of Recommendations Assessment, Development and Evaluation framework. Our primary outcome was live birth rate. Secondary outcomes included preeclampsia, preterm birth, intra-uterine growth restriction (IUGR) and thromboembolism. Safety outcomes included maternal or neonatal bleedings, heparin-induced thrombocytopenia and allergy. Subgroup analyses were conducted to explore heterogeneity. RESULTS: From 2395 identified citations, 13 trials (1916 patients) met inclusion criteria. Heparin, associated or not with aspirin, significantly increased the rate of live birth compared to any comparator (RR 1.20; 95 % CI 1.09-1.33},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: We performed a systematic review and meta-analysis to assess the efficacy and safety of heparin for preventing adverse obstetrical outcomes in pregnant women with antiphospholipid syndrome (APS).
METHODS: We reviewed randomized controlled trials from CENTRAL, EMBASE, MEDLINE, and Web of science (inception to November 5th 2019), and relevant article reference lists. Two reviewers independently screened and extracted data from trials investigating heparin, including Low Molecular Weight Heparin (LMWH) and unfractionated heparin (UFH) at any dose, associated or not with aspirin, compared to any comparator group in pregnant women with APS. Internal validity was assessed in duplicate using the Cochrane Risk of Bias tool. The strength of evidence was assessed in duplicate using the Grading of Recommendations Assessment, Development and Evaluation framework. Our primary outcome was live birth rate. Secondary outcomes included preeclampsia, preterm birth, intra-uterine growth restriction (IUGR) and thromboembolism. Safety outcomes included maternal or neonatal bleedings, heparin-induced thrombocytopenia and allergy. Subgroup analyses were conducted to explore heterogeneity. RESULTS: From 2395 identified citations, 13 trials (1916 patients) met inclusion criteria. Heparin, associated or not with aspirin, significantly increased the rate of live birth compared to any comparator (RR 1.20; 95 % CI 1.09-1.33 |
Fillion, Alexandre; Guerby, Paul; Lachance, Caroline; Comeau, Marie-Pier; Bussières, Marie-Claude; Doucet-Gingras, Félicia-Allysson; Zérounian, Sophie; Demers, Suzanne; Laforest, Geneviève; Menzies, Didier; Bujold, Emmanuel Placental Growth Factor and Soluble, Fms-Like Tyrosine Kinase-1 in Preeclampsia: A Case-Cohort (PEARL) Study Journal Article In: Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC, vol. 42, no. 10, pp. 1235–1242, 2020, ISSN: 1701-2163. @article{fillion_placental_2020,
title = {Placental Growth Factor and Soluble, Fms-Like Tyrosine Kinase-1 in Preeclampsia: A Case-Cohort (PEARL) Study},
author = {Fillion, Alexandre and Guerby, Paul and Lachance, Caroline and Comeau, Marie-Pier and Bussières, Marie-Claude and Doucet-Gingras, Félicia-Allysson and Zérounian, Sophie and Demers, Suzanne and Laforest, Geneviève and Menzies, Didier and Bujold, Emmanuel},
doi = {10.1016/j.jogc.2020.03.024},
issn = {1701-2163},
year = {2020},
date = {2020-10-01},
journal = {Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC},
volume = {42},
number = {10},
pages = {1235--1242},
abstract = {OBJECTIVE: Preeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia.
METHODS: We conducted a case-cohort study including low-risk nulliparous women recruited at 11-13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35-37 weeks) and late-onset (textgreater37 weeks) preeclampsia.
RESULTS: The cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25-38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P textless 0.05). We observed a significant difference between cases and controls, with a median ratio 100 times higher in early preeclampsia (P textless 0.001), 13 times higher in intermediate preeclampsia (P textless 0.001), but no significant difference between groups in late-onset preeclampsia with matched controls.
CONCLUSION: PlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Preeclampsia is associated with a higher maternal blood levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and lower levels of placental growth factor (PlGF) that appear before clinical onset. We aimed to estimate the normal progression of these biomarkers in normal pregnancies and in those affected by preeclampsia.
METHODS: We conducted a case-cohort study including low-risk nulliparous women recruited at 11-13 weeks gestation (cohort) and women with preeclampsia (cases). Maternal blood was collected at different points during pregnancy including at the time of diagnosis of preeclampsia for cases. Maternal serum PlGF and sFlt-1 concentrations and the sFlt-1/PlGF ratio were measured using B•R•A•H•M•S plus KRYPTOR automated assays and were compared between patients in both groups matched for gestational age. Cases were stratified as early- (≤34 weeks), intermediate- (35-37 weeks) and late-onset (textgreater37 weeks) preeclampsia.
RESULTS: The cohort consisted of 45 women whose results were compared with those of 31 women who developed preeclampsia, diagnosed at a median gestational age of 32 weeks (range 25-38 weeks). We observed that sFlt-1, PlGF and their ratio fluctuated during pregnancy in both groups, with a significant correlation with gestational age after 28 weeks (P textless 0.05). We observed a significant difference between cases and controls, with a median ratio 100 times higher in early preeclampsia (P textless 0.001), 13 times higher in intermediate preeclampsia (P textless 0.001), but no significant difference between groups in late-onset preeclampsia with matched controls.
CONCLUSION: PlGF, sFlt-1, and their ratio may be useful in the prediction and diagnosis of early- and intermediate-onset preeclampsia but are not useful for late-onset preeclampsia. |
Guerby, Paul; Bujold, Emmanuel How to calculate the risk of preeclampsia in women with a history of positive screening Journal Article In: American Journal of Obstetrics and Gynecology, vol. 223, no. 2, pp. 299–300, 2020, ISSN: 1097-6868. @article{guerby_how_2020,
title = {How to calculate the risk of preeclampsia in women with a history of positive screening},
author = {Guerby, Paul and Bujold, Emmanuel},
doi = {10.1016/j.ajog.2020.04.007},
issn = {1097-6868},
year = {2020},
date = {2020-08-01},
journal = {American Journal of Obstetrics and Gynecology},
volume = {223},
number = {2},
pages = {299--300},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Guerby, Paul; Bujold, Emmanuel Early Detection and Prevention of Intrauterine Growth Restriction and Its Consequences Journal Article In: JAMA pediatrics, vol. 174, no. 8, pp. 749–750, 2020, ISSN: 2168-6211. @article{guerby_early_2020,
title = {Early Detection and Prevention of Intrauterine Growth Restriction and Its Consequences},
author = {Guerby, Paul and Bujold, Emmanuel},
doi = {10.1001/jamapediatrics.2020.1106},
issn = {2168-6211},
year = {2020},
date = {2020-08-01},
journal = {JAMA pediatrics},
volume = {174},
number = {8},
pages = {749--750},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Monteiro, Renato; Tabiasco, Julie; Magerus, Aude; Gautreau-Rolland, Laetitia; Yssel, Hans French Immunology: from Louis Pasteur to present, always driving forward Journal Article In: European Journal of Immunology, vol. 50, no. 6, pp. 763–767, 2020, ISSN: 1521-4141. @article{monteiro_french_2020,
title = {French Immunology: from Louis Pasteur to present, always driving forward},
author = {Monteiro, Renato and Tabiasco, Julie and Magerus, Aude and Gautreau-Rolland, Laetitia and Yssel, Hans},
doi = {10.1002/eji.202070065},
issn = {1521-4141},
year = {2020},
date = {2020-06-01},
journal = {European Journal of Immunology},
volume = {50},
number = {6},
pages = {763--767},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Bahraoui, Elmostafa; Serrero, Manutea; Planès, Rémi HIV-1 Tat - TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-κB dependent pathway Journal Article In: Scientific Reports, vol. 10, no. 1, pp. 8177, 2020, ISSN: 2045-2322. @article{bahraoui_hiv-1_2020,
title = {HIV-1 Tat - TLR4/MD2 interaction drives the expression of IDO-1 in monocytes derived dendritic cells through NF-κB dependent pathway},
author = {Bahraoui, Elmostafa and Serrero, Manutea and Planès, Rémi},
doi = {10.1038/s41598-020-64847-y},
issn = {2045-2322},
year = {2020},
date = {2020-05-01},
journal = {Scientific Reports},
volume = {10},
number = {1},
pages = {8177},
abstract = {In the present study we showed that HIV-1 Tat protein stimulated the expression of Indoleamine 2,3 dioxygenase (IDO) -1 in human monocytes derived dendritic cells (MoDC) but not IDO-2 by acting directly at the cell membrane level. This induction of IDO-1 is dependent on the secondary structure of Tat protein, since stimulation with a chemically oxidized Tat protein loses its capacity to induce the production of IDO-1. Among the variety of candidate receptors described for Tat, we demonstrated that Tat protein interacted physically with TLR4/MD2 complex. Strikingly, blockade of Tat-TLR4 interaction by anti-TLR4 antibodies (clone HTA125), LPS-RS, a known TLR4 antagonist, or by soluble recombinant TLR4/MD2 complex inhibited strongly or totally the capacity of Tat to induce IDO-1 in MoDC while such treatments had no effect on IFN-γ-induced IDO-1. Furthermore, we showed that the activation of the transcription factor NF-κB by Tat is essential for the production of IDO-1 by human MoDC. Indeed, Tat activated NF-κB pathway in MoDC as demonstrated by the phosphorylation of p65 in Tat-treated MoDC. Further, we demonstrate that the stimulation of IDO-1 by Tat or by IFN-γ was totally or partially inhibited in the presence of NF-κB inhibitor respectively. These results suggest that Tat and IFN-γ act probably by two distinct mechanisms to induce the production of IDO-1. Our results clearly demonstrated that, although TLR4 pathway is necessary for Tat-induced IDO-1 in MoDC, it seems not to be sufficient since stable transfection of a functional TLR4/MD2 pathway in HEK or HeLa cell lines which are endogenously defectives for TLR4, did not restore the capacity of Tat to induce IDO-1 while IFN-γ treatment induces IDO-1 in HeLa cells independently of TLR4 pathway. These results suggest the involvement of additional stimuli in addition to TLR4 pathway which remain to be identified. Altogether our results demonstrated that, in human MoDC, HIV-1 Tat protein induced IDO-1 expression and activity in a NF-κB dependent-manner by recruiting TLR4 pathway.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the present study we showed that HIV-1 Tat protein stimulated the expression of Indoleamine 2,3 dioxygenase (IDO) -1 in human monocytes derived dendritic cells (MoDC) but not IDO-2 by acting directly at the cell membrane level. This induction of IDO-1 is dependent on the secondary structure of Tat protein, since stimulation with a chemically oxidized Tat protein loses its capacity to induce the production of IDO-1. Among the variety of candidate receptors described for Tat, we demonstrated that Tat protein interacted physically with TLR4/MD2 complex. Strikingly, blockade of Tat-TLR4 interaction by anti-TLR4 antibodies (clone HTA125), LPS-RS, a known TLR4 antagonist, or by soluble recombinant TLR4/MD2 complex inhibited strongly or totally the capacity of Tat to induce IDO-1 in MoDC while such treatments had no effect on IFN-γ-induced IDO-1. Furthermore, we showed that the activation of the transcription factor NF-κB by Tat is essential for the production of IDO-1 by human MoDC. Indeed, Tat activated NF-κB pathway in MoDC as demonstrated by the phosphorylation of p65 in Tat-treated MoDC. Further, we demonstrate that the stimulation of IDO-1 by Tat or by IFN-γ was totally or partially inhibited in the presence of NF-κB inhibitor respectively. These results suggest that Tat and IFN-γ act probably by two distinct mechanisms to induce the production of IDO-1. Our results clearly demonstrated that, although TLR4 pathway is necessary for Tat-induced IDO-1 in MoDC, it seems not to be sufficient since stable transfection of a functional TLR4/MD2 pathway in HEK or HeLa cell lines which are endogenously defectives for TLR4, did not restore the capacity of Tat to induce IDO-1 while IFN-γ treatment induces IDO-1 in HeLa cells independently of TLR4 pathway. These results suggest the involvement of additional stimuli in addition to TLR4 pathway which remain to be identified. Altogether our results demonstrated that, in human MoDC, HIV-1 Tat protein induced IDO-1 expression and activity in a NF-κB dependent-manner by recruiting TLR4 pathway. |
Berveiller, Paul; Guerby, Paul; Garabedian, Charles COVID19 and Breastfeeding: Not That Simple Journal Article In: Journal of Human Lactation: Official Journal of International Lactation Consultant Association, vol. 36, no. 2, pp. 369–370, 2020, ISSN: 1552-5732. @article{berveiller_covid19_2020,
title = {COVID19 and Breastfeeding: Not That Simple},
author = {Berveiller, Paul and Guerby, Paul and Garabedian, Charles},
doi = {10.1177/0890334420917102},
issn = {1552-5732},
year = {2020},
date = {2020-05-01},
journal = {Journal of Human Lactation: Official Journal of International Lactation Consultant Association},
volume = {36},
number = {2},
pages = {369--370},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Loussert, Lola; Vidal, Fabien; Parant, Olivier; Hamdi, Safouane M.; Vayssiere, Christophe; Guerby, Paul Aspirin for prevention of preeclampsia and fetal growth restriction Journal Article In: Prenatal Diagnosis, vol. 40, no. 5, pp. 519–527, 2020, ISSN: 1097-0223. @article{loussert_aspirin_2020,
title = {Aspirin for prevention of preeclampsia and fetal growth restriction},
author = {Loussert, Lola and Vidal, Fabien and Parant, Olivier and Hamdi, Safouane M. and Vayssiere, Christophe and Guerby, Paul},
doi = {10.1002/pd.5645},
issn = {1097-0223},
year = {2020},
date = {2020-04-01},
journal = {Prenatal Diagnosis},
volume = {40},
number = {5},
pages = {519--527},
abstract = {For the past decades, growing attention has been given to aspirin use during pregnancy. It favors placentation by its proangiogenic, antithrombotic, and anti-inflammatory effects. Therefore, low doses of aspirin are prescribed in the prevention of placenta-mediated complications, mainly preeclampsia and fetal growth restriction. However, questions regarding its clinical application are still debated. Aspirin is effective in preventing preeclampsia in a high-risk population. Most guidelines recommend that risk stratification should rely on medical history. Nevertheless, screening performances dramatically improve if biochemical and biophysical markers are included. Concerning the appropriate timing and dose, latest studies suggest aspirin should be started before 16 weeks of pregnancy and at a daily dose of 100 mg or more. Further studies are needed to improve the identification of patients likely to benefit from prophylactic aspirin. Besides, the role of aspirin in the prevention of fetal growth restriction is still questioned.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
For the past decades, growing attention has been given to aspirin use during pregnancy. It favors placentation by its proangiogenic, antithrombotic, and anti-inflammatory effects. Therefore, low doses of aspirin are prescribed in the prevention of placenta-mediated complications, mainly preeclampsia and fetal growth restriction. However, questions regarding its clinical application are still debated. Aspirin is effective in preventing preeclampsia in a high-risk population. Most guidelines recommend that risk stratification should rely on medical history. Nevertheless, screening performances dramatically improve if biochemical and biophysical markers are included. Concerning the appropriate timing and dose, latest studies suggest aspirin should be started before 16 weeks of pregnancy and at a daily dose of 100 mg or more. Further studies are needed to improve the identification of patients likely to benefit from prophylactic aspirin. Besides, the role of aspirin in the prevention of fetal growth restriction is still questioned. |
Negre-Salvayre, Anne; Guerby, Paul; Gayral, Stephanie; Laffargue, Muriel; Salvayre, Robert Role of reactive oxygen species in atherosclerosis: Lessons from murine genetic models Journal Article In: Free Radical Biology & Medicine, vol. 149, pp. 8–22, 2020, ISSN: 1873-4596. @article{negre-salvayre_role_2020,
title = {Role of reactive oxygen species in atherosclerosis: Lessons from murine genetic models},
author = {Negre-Salvayre, Anne and Guerby, Paul and Gayral, Stephanie and Laffargue, Muriel and Salvayre, Robert},
doi = {10.1016/j.freeradbiomed.2019.10.011},
issn = {1873-4596},
year = {2020},
date = {2020-03-01},
journal = {Free Radical Biology & Medicine},
volume = {149},
pages = {8--22},
abstract = {Atherosclerosis is a multifactorial chronic and inflammatory disease of medium and large arteries, and the major cause of cardiovascular morbidity and mortality worldwide. The pathogenesis of atherosclerosis involves a number of risk factors and complex events including hypercholesterolemia, endothelial dysfunction, increased permeability to low density lipoproteins (LDL) and their sequestration on extracellular matrix in the intima of lesion-prone areas. These events promote LDL modifications, particularly by oxidation, which generates acute and chronic inflammatory responses implicated in atherogenesis and lesion progression. Reactive oxygen species (ROS) (which include both free radical and non-free radical oxygen intermediates), play a key-role at each step of atherogenesis, in endothelial dysfunction, LDL oxidation, and inflammatory events involved in the initiation and development of atherosclerosis lesions. Most advanced knowledge supporting the "oxidative theory of atherosclerosis" i.e. the nature and the cellular sources of ROS and antioxidant defences, as well as the mechanisms involved in the redox balance, is based on the use of genetically engineered animals, i.e. transgenic, genetically modified, or altered for systems producing or neutralizing ROS in the vessels. This review summarizes the results obtained from animals genetically manipulated for various sources of ROS or antioxidant defences in the vascular wall, and their relevance (advance or limitation), for understanding the place and role of ROS in atherosclerosis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Atherosclerosis is a multifactorial chronic and inflammatory disease of medium and large arteries, and the major cause of cardiovascular morbidity and mortality worldwide. The pathogenesis of atherosclerosis involves a number of risk factors and complex events including hypercholesterolemia, endothelial dysfunction, increased permeability to low density lipoproteins (LDL) and their sequestration on extracellular matrix in the intima of lesion-prone areas. These events promote LDL modifications, particularly by oxidation, which generates acute and chronic inflammatory responses implicated in atherogenesis and lesion progression. Reactive oxygen species (ROS) (which include both free radical and non-free radical oxygen intermediates), play a key-role at each step of atherogenesis, in endothelial dysfunction, LDL oxidation, and inflammatory events involved in the initiation and development of atherosclerosis lesions. Most advanced knowledge supporting the "oxidative theory of atherosclerosis" i.e. the nature and the cellular sources of ROS and antioxidant defences, as well as the mechanisms involved in the redox balance, is based on the use of genetically engineered animals, i.e. transgenic, genetically modified, or altered for systems producing or neutralizing ROS in the vessels. This review summarizes the results obtained from animals genetically manipulated for various sources of ROS or antioxidant defences in the vascular wall, and their relevance (advance or limitation), for understanding the place and role of ROS in atherosclerosis. |
Blondy, Thibaut; d'Almeida, Sènan Mickael; Briolay, Tina; Tabiasco, Julie; Meiller, Clément; Chéné, Anne-Laure; Cellerin, Laurent; Deshayes, Sophie; Delneste, Yves; Fonteneau, Jean-François; Boisgerault, Nicolas; Bennouna, Jaafar; Grégoire, Marc; Jean, Didier; Blanquart, Christophe Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma Journal Article In: Journal for Immunotherapy of Cancer, vol. 8, no. 1, 2020, ISSN: 2051-1426. @article{blondy_involvement_2020,
title = {Involvement of the M-CSF/IL-34/CSF-1R pathway in malignant pleural mesothelioma},
author = {Blondy, Thibaut and d'Almeida, Sènan Mickael and Briolay, Tina and Tabiasco, Julie and Meiller, Clément and Chéné, Anne-Laure and Cellerin, Laurent and Deshayes, Sophie and Delneste, Yves and Fonteneau, Jean-François and Boisgerault, Nicolas and Bennouna, Jaafar and Grégoire, Marc and Jean, Didier and Blanquart, Christophe},
doi = {10.1136/jitc-2019-000182},
issn = {2051-1426},
year = {2020},
date = {2020-01-01},
journal = {Journal for Immunotherapy of Cancer},
volume = {8},
number = {1},
abstract = {BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The tumor microenvironment content, particularly the presence of macrophages, was described as crucial for the development of the disease. This work aimed at studying the involvement of the M-CSF (CSF-1)/IL-34/CSF-1R pathway in the formation of macrophages in MPM, using samples from patients.
METHODS: Pleural effusions (PEs), frozen tumors, primary MPM cells and MPM cell lines used in this study belong to biocollections associated with clinical databases. Cytokine expressions were studied using real-time PCR and ELISA. The Cancer Genome Atlas database was used to confirm our results on an independent cohort. An original three-dimensional (3D) coculture model including MPM cells, monocytes from healthy donors and a tumor antigen-specific cytotoxic CD8 T cell clone was used.
RESULTS: We observed that high interleukin (IL)-34 levels in PE were significantly associated with a shorter survival of patients. In tumors, expression of CSF1 was correlated with 'M2-like macrophages' markers, whereas this was not the case with IL34 expression, suggesting two distinct modes of action of these cytokines. Expression of IL34 was higher in MPM cells compared with primary mesothelial cells. Particularly, high expression of IL34 was observed in MPM cells with an alteration of CDKN2A. Finally, using 3D coculture model, we demonstrated the direct involvement of MPM cells in the formation of immunosuppressive macrophages, through activation of the colony stimulating factor-1 receptor (CSF1-R) pathway, causing the inhibition of cytotoxicity of tumor antigen-specific CD8+ T cells.
CONCLUSIONS: The M-CSF/IL-34/CSF-1R pathway seems strongly implicated in MPM and could constitute a therapeutic target to act on immunosuppression and to support immunotherapeutic strategies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Malignant pleural mesothelioma (MPM) is a rare and aggressive cancer related to asbestos exposure. The tumor microenvironment content, particularly the presence of macrophages, was described as crucial for the development of the disease. This work aimed at studying the involvement of the M-CSF (CSF-1)/IL-34/CSF-1R pathway in the formation of macrophages in MPM, using samples from patients.
METHODS: Pleural effusions (PEs), frozen tumors, primary MPM cells and MPM cell lines used in this study belong to biocollections associated with clinical databases. Cytokine expressions were studied using real-time PCR and ELISA. The Cancer Genome Atlas database was used to confirm our results on an independent cohort. An original three-dimensional (3D) coculture model including MPM cells, monocytes from healthy donors and a tumor antigen-specific cytotoxic CD8 T cell clone was used.
RESULTS: We observed that high interleukin (IL)-34 levels in PE were significantly associated with a shorter survival of patients. In tumors, expression of CSF1 was correlated with 'M2-like macrophages' markers, whereas this was not the case with IL34 expression, suggesting two distinct modes of action of these cytokines. Expression of IL34 was higher in MPM cells compared with primary mesothelial cells. Particularly, high expression of IL34 was observed in MPM cells with an alteration of CDKN2A. Finally, using 3D coculture model, we demonstrated the direct involvement of MPM cells in the formation of immunosuppressive macrophages, through activation of the colony stimulating factor-1 receptor (CSF1-R) pathway, causing the inhibition of cytotoxicity of tumor antigen-specific CD8+ T cells.
CONCLUSIONS: The M-CSF/IL-34/CSF-1R pathway seems strongly implicated in MPM and could constitute a therapeutic target to act on immunosuppression and to support immunotherapeutic strategies. |
Boutin, Amélie; Guerby, Paul; Gasse, Cédric; Tapp, Sylvie; Bujold, Emmanuel Pregnancy outcomes in nulliparous women with positive first-trimester preterm preeclampsia screening test: the Great Obstetrical Syndromes cohort study Journal Article In: American Journal of Obstetrics and Gynecology, 2020, ISSN: 1097-6868. @article{boutin_pregnancy_2020,
title = {Pregnancy outcomes in nulliparous women with positive first-trimester preterm preeclampsia screening test: the Great Obstetrical Syndromes cohort study},
author = {Boutin, Amélie and Guerby, Paul and Gasse, Cédric and Tapp, Sylvie and Bujold, Emmanuel},
doi = {10.1016/j.ajog.2020.08.008},
issn = {1097-6868},
year = {2020},
date = {2020-01-01},
journal = {American Journal of Obstetrics and Gynecology},
abstract = {BACKGROUND: The Fetal Medicine Foundation proposed a competing risks model for early identification of women at a high risk of preterm preeclampsia, typically associated with deep placentation disorders. The Great Obstetrical Syndromes include a spectrum of pregnancy complications (preeclampsia, intrauterine growth restriction, preterm birth, late spontaneous abortion, and abruptio placentae) that are also associated with deep placentation disorders.
OBJECTIVE: This study aimed to estimate the rate of placenta-mediated pregnancy complications in nulliparous women with a positive first-trimester Fetal Medicine Foundation preterm preeclampsia screening test.
STUDY DESIGN: We conducted a prospective cohort study of nulliparous women recruited at 11 to 14 weeks of gestation. Maternal characteristics, mean arterial blood pressure, levels of maternal serum biomarkers (pregnancy-associated plasma protein-A, placental growth factor, and soluble fms-like tyrosine kinase-1), and mean uterine artery pulsatility index were obtained to calculate the risk of preterm preeclampsia according to the Fetal Medicine Foundation algorithm. The predicted risks were dichotomized as a positive or negative test according to 2 risk cutoffs (1 in 70 and 1 in 100). The detection rate, false-positive rate, and positive and negative predictive values were calculated for placenta-mediated complications, including preeclampsia, small for gestational age (birthweight textless10th percentile), fetal death, preterm birth, and a composite outcome, including any of the foregoing. The same analyses were computed for a composite of severe outcomes, including preterm preeclampsia, severe small for gestational age (less than third percentile), and fetal death.
RESULTS: We included 4575 participants with complete observations, of whom 494 (10.8%) had an estimated risk of preterm preeclampsia of ≥1 in 70 and 728 (15.9%) had a risk of ≥1 in 100. The test based on a risk cutoff of 1 in 70 could have correctly predicted up to 27% of preeclampsia, 55% of preterm preeclampsia, 18% of small for gestational age, 24% of severe small for gestational age, and 37% of fetal deaths at a 10% false-positive rate. The test based on a cutoff of 1 in 100 could have predicted correctly up to 35% of preeclampsia, 69% of preterm preeclampsia, 25% of small for gestational age, 30% of severe small for gestational age, and 53% of fetal deaths at a 15% false-positive rate. The positive predictive value of a screening test for preterm preeclampsia of ≥1 in 70 was 3% for preterm preeclampsia, 32% for the composite outcome, and 9% for the severe composite outcome.
CONCLUSION: Nulliparous women with a first-trimester positive preterm preeclampsia Fetal Medicine Foundation screening test are at a higher risk of both preterm preeclampsia and other severe placenta-mediated pregnancy complications. Approximately 1 woman of 10 identified as high risk by the Fetal Medicine Foundation algorithm developed at least 1 severe placenta-mediated pregnancy complication.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: The Fetal Medicine Foundation proposed a competing risks model for early identification of women at a high risk of preterm preeclampsia, typically associated with deep placentation disorders. The Great Obstetrical Syndromes include a spectrum of pregnancy complications (preeclampsia, intrauterine growth restriction, preterm birth, late spontaneous abortion, and abruptio placentae) that are also associated with deep placentation disorders.
OBJECTIVE: This study aimed to estimate the rate of placenta-mediated pregnancy complications in nulliparous women with a positive first-trimester Fetal Medicine Foundation preterm preeclampsia screening test.
STUDY DESIGN: We conducted a prospective cohort study of nulliparous women recruited at 11 to 14 weeks of gestation. Maternal characteristics, mean arterial blood pressure, levels of maternal serum biomarkers (pregnancy-associated plasma protein-A, placental growth factor, and soluble fms-like tyrosine kinase-1), and mean uterine artery pulsatility index were obtained to calculate the risk of preterm preeclampsia according to the Fetal Medicine Foundation algorithm. The predicted risks were dichotomized as a positive or negative test according to 2 risk cutoffs (1 in 70 and 1 in 100). The detection rate, false-positive rate, and positive and negative predictive values were calculated for placenta-mediated complications, including preeclampsia, small for gestational age (birthweight textless10th percentile), fetal death, preterm birth, and a composite outcome, including any of the foregoing. The same analyses were computed for a composite of severe outcomes, including preterm preeclampsia, severe small for gestational age (less than third percentile), and fetal death.
RESULTS: We included 4575 participants with complete observations, of whom 494 (10.8%) had an estimated risk of preterm preeclampsia of ≥1 in 70 and 728 (15.9%) had a risk of ≥1 in 100. The test based on a risk cutoff of 1 in 70 could have correctly predicted up to 27% of preeclampsia, 55% of preterm preeclampsia, 18% of small for gestational age, 24% of severe small for gestational age, and 37% of fetal deaths at a 10% false-positive rate. The test based on a cutoff of 1 in 100 could have predicted correctly up to 35% of preeclampsia, 69% of preterm preeclampsia, 25% of small for gestational age, 30% of severe small for gestational age, and 53% of fetal deaths at a 15% false-positive rate. The positive predictive value of a screening test for preterm preeclampsia of ≥1 in 70 was 3% for preterm preeclampsia, 32% for the composite outcome, and 9% for the severe composite outcome.
CONCLUSION: Nulliparous women with a first-trimester positive preterm preeclampsia Fetal Medicine Foundation screening test are at a higher risk of both preterm preeclampsia and other severe placenta-mediated pregnancy complications. Approximately 1 woman of 10 identified as high risk by the Fetal Medicine Foundation algorithm developed at least 1 severe placenta-mediated pregnancy complication. |
Tasta, Oriane; Parant, Olivier; Hamdi, Safouane M.; Allouche, Mickael; Vayssiere, Christophe; Guerby, Paul Evaluation of the Prognostic Value of the sFlt-1/PlGF Ratio in Early-Onset Preeclampsia Journal Article In: American Journal of Perinatology, 2020, ISSN: 1098-8785. @article{tasta_evaluation_2020,
title = {Evaluation of the Prognostic Value of the sFlt-1/PlGF Ratio in Early-Onset Preeclampsia},
author = {Tasta, Oriane and Parant, Olivier and Hamdi, Safouane M. and Allouche, Mickael and Vayssiere, Christophe and Guerby, Paul},
doi = {10.1055/s-0040-1709696},
issn = {1098-8785},
year = {2020},
date = {2020-01-01},
journal = {American Journal of Perinatology},
abstract = {OBJECTIVE: Increased expression of soluble fms-like tyrosine kinase 1 (sFlt-1), associated with a decrease in placental growth factor (PlGF), plays a key role in the pathogenesis of preeclampsia (PE). We evaluated the prognostic value of the sFlt-1/PlGF ratio for the onset of adverse maternofetal outcomes (AMFO) in case of early-onset PE with attempted expectant management.
STUDY DESIGN: From October 2016 through November 2018, all singleton pregnancies complicated by early-onset PE (before 34 weeks of gestation) were included in a cohort study. The plasma levels of sFlt-1 and PlGF were blindly measured on admission. For the statistical analysis, we performed a bivariate analysis, a comparison of the receiving operating characteristic curves and a survival analysis estimated by the Kaplan-Meier method. RESULTS: Among 109 early PE, AMFO occurred in 87 pregnancies (79.8%), mainly hemolysis, elevated liver enzymes, and low platelet count syndrome and severe fetal heart rate abnormalities requiring urgent delivery. The area under the curve (AUC) of sFlt-1/PlGF ratio was 0.82 (95% confidence interval [CI]: 0.73-0.88) for the risk of AMFO and the difference between the AUCs was significant for each separate standard parameter (p = 0.018 for initial diastolic blood pressure, p = 0.013 for alanine aminotransferase, p textless 0.001 for uric acid). Pregnancies were best classified by a cutoff ratio of 293, with a sensitivity of 95% and a specificity of 50%. With a ratio value less than 293, no pregnancy was complicated or had been stopped during the first 5 days. A ratio more than 293 was associated with an increased risk of AMFO onset (hazard ratio [HR]: 3.61; 95% CI: 2.13-6.10; p textless 0.001) and had a significant association with the length of time between the diagnosis of PE and delivery (HR: 2.49; 95% CI: 1.56-3.96; p textless 0.001).
CONCLUSION: The sFlt-1/PlGF ratio is an additional tool in the prediction of AMFO in proven early-onset PE, which is likely to improve care by anticipating severe complications.
KEY POINTS: · The sFlt-1/PlGF ratio is associated with AMFO.. · It is an additional tool for physician.. · We proposed a 293 cutoff value for the ratio..},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Increased expression of soluble fms-like tyrosine kinase 1 (sFlt-1), associated with a decrease in placental growth factor (PlGF), plays a key role in the pathogenesis of preeclampsia (PE). We evaluated the prognostic value of the sFlt-1/PlGF ratio for the onset of adverse maternofetal outcomes (AMFO) in case of early-onset PE with attempted expectant management.
STUDY DESIGN: From October 2016 through November 2018, all singleton pregnancies complicated by early-onset PE (before 34 weeks of gestation) were included in a cohort study. The plasma levels of sFlt-1 and PlGF were blindly measured on admission. For the statistical analysis, we performed a bivariate analysis, a comparison of the receiving operating characteristic curves and a survival analysis estimated by the Kaplan-Meier method. RESULTS: Among 109 early PE, AMFO occurred in 87 pregnancies (79.8%), mainly hemolysis, elevated liver enzymes, and low platelet count syndrome and severe fetal heart rate abnormalities requiring urgent delivery. The area under the curve (AUC) of sFlt-1/PlGF ratio was 0.82 (95% confidence interval [CI]: 0.73-0.88) for the risk of AMFO and the difference between the AUCs was significant for each separate standard parameter (p = 0.018 for initial diastolic blood pressure, p = 0.013 for alanine aminotransferase, p textless 0.001 for uric acid). Pregnancies were best classified by a cutoff ratio of 293, with a sensitivity of 95% and a specificity of 50%. With a ratio value less than 293, no pregnancy was complicated or had been stopped during the first 5 days. A ratio more than 293 was associated with an increased risk of AMFO onset (hazard ratio [HR]: 3.61; 95% CI: 2.13-6.10; p textless 0.001) and had a significant association with the length of time between the diagnosis of PE and delivery (HR: 2.49; 95% CI: 1.56-3.96; p textless 0.001).
CONCLUSION: The sFlt-1/PlGF ratio is an additional tool in the prediction of AMFO in proven early-onset PE, which is likely to improve care by anticipating severe complications.
KEY POINTS: · The sFlt-1/PlGF ratio is associated with AMFO.. · It is an additional tool for physician.. · We proposed a 293 cutoff value for the ratio.. |
Guerby, Paul; Sartor, Agnès; Vidal, Fabien; Vayssière, Christophe Selective feticide as a treatment of severe preeclampsia in discordant twins Journal Article In: Journal of Gynecology Obstetrics and Human Reproduction, vol. 49, no. 1, pp. 101633, 2020, ISSN: 2468-7847. @article{guerby_selective_2020,
title = {Selective feticide as a treatment of severe preeclampsia in discordant twins},
author = {Guerby, Paul and Sartor, Agnès and Vidal, Fabien and Vayssière, Christophe},
doi = {10.1016/j.jogoh.2019.101633},
issn = {2468-7847},
year = {2020},
date = {2020-01-01},
journal = {Journal of Gynecology Obstetrics and Human Reproduction},
volume = {49},
number = {1},
pages = {101633},
abstract = {Multifetal gestation is often complicated by the development of preeclampsia. In some twin gestations, preeclampsia develops in association with restricted fetal growth of only one fetus. Instead of termination of the entire pregnancy, we investigated an alternative approach to the management of such pregnancies that might allow unharmed survival of the normal twin. We present a case of preeclampsia in twin discordance with severe fetal growth restriction at 25 weeks of gestation. Preeclampsia was linked to a lethal condition in one twin and was treated with selective feticide in an effort to reverse preeclampsia. Inasmuch as the fetal prognosis was extremely poor for the abnormal fetus, selective feticide was a reasonable therapeutic option. Maternal symptoms resolved, allowing continuation of the pregnancy for 4 weeks before delivery of the healthy fetus. We maintain that selective termination induced a decrease in the release of substances involved in the physiopathology of preeclampsia, which allowed the continuation of the pregnancy with close follow-up. This report highlights the link between placental pathology and the disease process of preeclampsia and further supports selective termination as a reasonable management strategy in carefully selected cases of discordant twins.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Multifetal gestation is often complicated by the development of preeclampsia. In some twin gestations, preeclampsia develops in association with restricted fetal growth of only one fetus. Instead of termination of the entire pregnancy, we investigated an alternative approach to the management of such pregnancies that might allow unharmed survival of the normal twin. We present a case of preeclampsia in twin discordance with severe fetal growth restriction at 25 weeks of gestation. Preeclampsia was linked to a lethal condition in one twin and was treated with selective feticide in an effort to reverse preeclampsia. Inasmuch as the fetal prognosis was extremely poor for the abnormal fetus, selective feticide was a reasonable therapeutic option. Maternal symptoms resolved, allowing continuation of the pregnancy for 4 weeks before delivery of the healthy fetus. We maintain that selective termination induced a decrease in the release of substances involved in the physiopathology of preeclampsia, which allowed the continuation of the pregnancy with close follow-up. This report highlights the link between placental pathology and the disease process of preeclampsia and further supports selective termination as a reasonable management strategy in carefully selected cases of discordant twins. |
2019
|
Guerby, Paul; Swiader, Audrey; Tasta, Oriane; Pont, Frédéric; Rodriguez, Frédéric; Parant, Olivier; Vayssière, Christophe; Shibata, Takahiro; Uchida, Koji; Salvayre, Robert; Negre-Salvayre, Anne Modification of endothelial nitric oxide synthase by 4-oxo-2(E)-nonenal(ONE) in preeclamptic placentas Journal Article In: Free Radical Biology & Medicine, vol. 141, pp. 416–425, 2019, ISSN: 1873-4596. @article{guerby_modification_2019,
title = {Modification of endothelial nitric oxide synthase by 4-oxo-2(E)-nonenal(ONE) in preeclamptic placentas},
author = {Guerby, Paul and Swiader, Audrey and Tasta, Oriane and Pont, Frédéric and Rodriguez, Frédéric and Parant, Olivier and Vayssière, Christophe and Shibata, Takahiro and Uchida, Koji and Salvayre, Robert and Negre-Salvayre, Anne},
doi = {10.1016/j.freeradbiomed.2019.07.015},
issn = {1873-4596},
year = {2019},
date = {2019-09-01},
journal = {Free Radical Biology & Medicine},
volume = {141},
pages = {416--425},
abstract = {Preeclampsia (PE) is a leading cause of pregnancy complications, affecting 3-7% of pregnant women worldwide. The pathophysiology of preeclampsia involves a redox imbalance, oxidative stress and a reduced nitric oxide (NO) bioavailability. The molecular and cellular mechanisms leading to the dysfunction of the placental endothelial NO synthase (eNOS) are not clarified. This study was designed to investigate whether aldehydes generated by lipid peroxidation products (LPP), may contribute to placental eNOS dysfunction in PE. The analysis of placentas from PE-affected patients and normal pregnancies, showed a significant increase in protein carbonyl content, indicative of oxidative stress-induced protein modification, as shown by the accumulation of acrolein, 4-hydroxynonenal (HNE), and 4-oxo-2(E)-nonenal (ONE) adducts in PE placentas. In contrast, the levels of these LPP-adducts were low in placentas from normal pregnancies. Immunofluorescence and confocal experiments pointed out a colocalization of eNOS with ONE-Lys adducts, whereas eNOS was not modified in normal placentas. LC-MS/MS analysis of recombinant eNOS preincubated with ONE, allowed to identify several ONE-modified Lys-containing peptides, confirming that eNOS may undergo post-translational modification by LPP. The preincubation of HTR-8/SVneo human trophoblasts (HTR8) with ONE, resulted in ONE-Lys modification of eNOS and a reduced generation of NO. ONE inhibited the migration of HTR8 trophoblasts in the wound closure model, and this was partly restored by the NO donor, NOC-18, which confirmed the important role of NO in the invasive potential of trophoblasts. In conclusion, placental eNOS is modified by ONE in PE placentas, which emphasizes the sensitivity of this protein to oxidative stress in the disturbed redox environment of preeclamptic pregnancies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Preeclampsia (PE) is a leading cause of pregnancy complications, affecting 3-7% of pregnant women worldwide. The pathophysiology of preeclampsia involves a redox imbalance, oxidative stress and a reduced nitric oxide (NO) bioavailability. The molecular and cellular mechanisms leading to the dysfunction of the placental endothelial NO synthase (eNOS) are not clarified. This study was designed to investigate whether aldehydes generated by lipid peroxidation products (LPP), may contribute to placental eNOS dysfunction in PE. The analysis of placentas from PE-affected patients and normal pregnancies, showed a significant increase in protein carbonyl content, indicative of oxidative stress-induced protein modification, as shown by the accumulation of acrolein, 4-hydroxynonenal (HNE), and 4-oxo-2(E)-nonenal (ONE) adducts in PE placentas. In contrast, the levels of these LPP-adducts were low in placentas from normal pregnancies. Immunofluorescence and confocal experiments pointed out a colocalization of eNOS with ONE-Lys adducts, whereas eNOS was not modified in normal placentas. LC-MS/MS analysis of recombinant eNOS preincubated with ONE, allowed to identify several ONE-modified Lys-containing peptides, confirming that eNOS may undergo post-translational modification by LPP. The preincubation of HTR-8/SVneo human trophoblasts (HTR8) with ONE, resulted in ONE-Lys modification of eNOS and a reduced generation of NO. ONE inhibited the migration of HTR8 trophoblasts in the wound closure model, and this was partly restored by the NO donor, NOC-18, which confirmed the important role of NO in the invasive potential of trophoblasts. In conclusion, placental eNOS is modified by ONE in PE placentas, which emphasizes the sensitivity of this protein to oxidative stress in the disturbed redox environment of preeclamptic pregnancies. |
Guerby, Paul; Swiader, Audrey; Augé, Nathalie; Parant, Olivier; Vayssière, Christophe; Uchida, Koji; Salvayre, Robert; Negre-Salvayre, Anne High glutathionylation of placental endothelial nitric oxide synthase in preeclampsia Journal Article In: Redox Biology, vol. 22, pp. 101126, 2019, ISSN: 2213-2317. @article{guerby_high_2019,
title = {High glutathionylation of placental endothelial nitric oxide synthase in preeclampsia},
author = {Guerby, Paul and Swiader, Audrey and Augé, Nathalie and Parant, Olivier and Vayssière, Christophe and Uchida, Koji and Salvayre, Robert and Negre-Salvayre, Anne},
doi = {10.1016/j.redox.2019.101126},
issn = {2213-2317},
year = {2019},
date = {2019-04-01},
journal = {Redox Biology},
volume = {22},
pages = {101126},
abstract = {Decreased nitric oxide (NO) bioavailability plays a critical role in the pathophysiology of preeclampsia (PE). Recent evidence indicates that S-glutathionylation may occur on the endothelial nitric oxide synthase (eNOS), leading to eNOS uncoupling, characterized by a decreased NO production and an increased generation of superoxide anion (O2•-). We hypothesized that eNOS glutathionylation may occur in PE placentas and participate in eNOS dysfunction. The glutathionylation of eNOS was investigated in thirteen PE-affected patients and in nine normal pregnancies. Immunofluorescence, confocal microscopy and western-blot experiments carried out on eNOS immunoprecipitates, revealed a high level of eNOS glutathionylation in PE placentas, mostly reversed by dithiotreitol (DTT), thus indicative of S-glutathionylation. In order to investigate whether eNOS glutathionylation may alter trophoblast migration, an important event occurring during early placentation, cultured HTR-8/SVneo human trophoblasts (HTR8) were exposed either to low pO2 (O2 1%) or to pO2 changes (O2 1-20%), in order to generate oxidative stress. Trophoblasts exposed to low pO2, did not undergo oxidative stress nor eNOS S-glutathionylation, and were able to generate NO and migrate in a wound closure model. In contrast, trophoblasts submitted to low/high pO2 changes, exhibited oxidative stress and a (DTT reversible) S-glutathionylation of eNOS, associated with reduced NO production and migration. The autonomous production of NO seemed necessary for the migratory potential of HTR8, as suggested by the inhibitory effect of eNOS silencing by small interfering RNAs, and the eNOS inhibitor L-NAME, in low pO2 conditions. Finally, the addition of the NO donor, NOC-18 (5 µM), restored in part the migration of HTR8, thereby emphasizing the role of NO in trophoblast homeostasis. In conclusion, the high level of eNOS S-glutathionylation in PE placentas provides new insights in the mechanism of eNOS dysfunction in this disease.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Decreased nitric oxide (NO) bioavailability plays a critical role in the pathophysiology of preeclampsia (PE). Recent evidence indicates that S-glutathionylation may occur on the endothelial nitric oxide synthase (eNOS), leading to eNOS uncoupling, characterized by a decreased NO production and an increased generation of superoxide anion (O2•-). We hypothesized that eNOS glutathionylation may occur in PE placentas and participate in eNOS dysfunction. The glutathionylation of eNOS was investigated in thirteen PE-affected patients and in nine normal pregnancies. Immunofluorescence, confocal microscopy and western-blot experiments carried out on eNOS immunoprecipitates, revealed a high level of eNOS glutathionylation in PE placentas, mostly reversed by dithiotreitol (DTT), thus indicative of S-glutathionylation. In order to investigate whether eNOS glutathionylation may alter trophoblast migration, an important event occurring during early placentation, cultured HTR-8/SVneo human trophoblasts (HTR8) were exposed either to low pO2 (O2 1%) or to pO2 changes (O2 1-20%), in order to generate oxidative stress. Trophoblasts exposed to low pO2, did not undergo oxidative stress nor eNOS S-glutathionylation, and were able to generate NO and migrate in a wound closure model. In contrast, trophoblasts submitted to low/high pO2 changes, exhibited oxidative stress and a (DTT reversible) S-glutathionylation of eNOS, associated with reduced NO production and migration. The autonomous production of NO seemed necessary for the migratory potential of HTR8, as suggested by the inhibitory effect of eNOS silencing by small interfering RNAs, and the eNOS inhibitor L-NAME, in low pO2 conditions. Finally, the addition of the NO donor, NOC-18 (5 µM), restored in part the migration of HTR8, thereby emphasizing the role of NO in trophoblast homeostasis. In conclusion, the high level of eNOS S-glutathionylation in PE placentas provides new insights in the mechanism of eNOS dysfunction in this disease. |
Staerck, Cindy; Tabiasco, Julie; Godon, Charlotte; Delneste, Yves; Bouchara, Jean-Philippe; Fleury, Maxime J. J. Transcriptional profiling of Scedosporium apiospermum enzymatic antioxidant gene battery unravels the involvement of thioredoxin reductases against chemical and phagocytic cells oxidative stress Journal Article In: Medical Mycology, vol. 57, no. 3, pp. 363–373, 2019, ISSN: 1460-2709. @article{staerck_transcriptional_2019,
title = {Transcriptional profiling of Scedosporium apiospermum enzymatic antioxidant gene battery unravels the involvement of thioredoxin reductases against chemical and phagocytic cells oxidative stress},
author = {Staerck, Cindy and Tabiasco, Julie and Godon, Charlotte and Delneste, Yves and Bouchara, Jean-Philippe and Fleury, Maxime J. J.},
doi = {10.1093/mmy/myy033},
issn = {1460-2709},
year = {2019},
date = {2019-01-01},
journal = {Medical Mycology},
volume = {57},
number = {3},
pages = {363--373},
abstract = {Scedosporium species rank the second, after Aspergillus fumigatus, among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Development of microorganisms in the respiratory tract depends on their capacity to evade killing by the host immune system, particularly through the oxidative response of macrophages and neutrophils, with the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS). This is particularly true in the airways of CF patients which display an exacerbated inflammatory reaction. To protect themselves, pathogens have developed various enzymatic antioxidant systems implicated in ROS degradation, including superoxide dismutases, catalases, cytochrome C peroxidases, chloroperoxidases and enzymes of the glutathione and thioredoxin systems, or in RNS degradation, that is, flavohemoglobins, nitrate reductases, and nitrite reductases. Here we investigated the transcriptional regulation of the enzymatic antioxidant gene battery in 24-h-old hyphae of Scedosporium apiospermum in response to oxidative stress induced chemically or by exposure to activated phagocytic cells. We showed that 21 out of the 33 genes potentially implicated in the oxidative or nitrosative stress response were overexpressed upon exposure of the fungus to various chemical oxidants, while they were only 13 in co-cultures with macrophages or neutrophils. Among them, genes encoding two thioredoxin reductases and to a lesser extent, a peroxiredoxin and one catalase were found to be overexpressed after chemical oxidative stress as well as in co-cultures. These results suggest that thioredoxin reductases, which are known to be virulence factors in other pathogenic fungi, play a key role in pathogenesis of scedosporiosis, and may be new drug targets.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Scedosporium species rank the second, after Aspergillus fumigatus, among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Development of microorganisms in the respiratory tract depends on their capacity to evade killing by the host immune system, particularly through the oxidative response of macrophages and neutrophils, with the release of reactive oxygen species (ROS) and reactive nitrogen species (RNS). This is particularly true in the airways of CF patients which display an exacerbated inflammatory reaction. To protect themselves, pathogens have developed various enzymatic antioxidant systems implicated in ROS degradation, including superoxide dismutases, catalases, cytochrome C peroxidases, chloroperoxidases and enzymes of the glutathione and thioredoxin systems, or in RNS degradation, that is, flavohemoglobins, nitrate reductases, and nitrite reductases. Here we investigated the transcriptional regulation of the enzymatic antioxidant gene battery in 24-h-old hyphae of Scedosporium apiospermum in response to oxidative stress induced chemically or by exposure to activated phagocytic cells. We showed that 21 out of the 33 genes potentially implicated in the oxidative or nitrosative stress response were overexpressed upon exposure of the fungus to various chemical oxidants, while they were only 13 in co-cultures with macrophages or neutrophils. Among them, genes encoding two thioredoxin reductases and to a lesser extent, a peroxiredoxin and one catalase were found to be overexpressed after chemical oxidative stress as well as in co-cultures. These results suggest that thioredoxin reductases, which are known to be virulence factors in other pathogenic fungi, play a key role in pathogenesis of scedosporiosis, and may be new drug targets. |
Dukhovny, A.; Lamkiewicz, K.; Chen, Q.; Fricke, M.; Jabrane-Ferrat, N.; Marz, M.; Jung, J. U.; Sklan, E. H. A CRISPR Activation Screen Identifies Genes That Protect against Zika Virus Infection Journal Article In: J Virol, vol. 93, no. 16, 2019, ISSN: 1098-5514 (Electronic) 0022-538X (Linking). @article{dukhovny_crispr_2019,
title = {A CRISPR Activation Screen Identifies Genes That Protect against Zika Virus Infection},
author = {Dukhovny, A. and Lamkiewicz, K. and Chen, Q. and Fricke, M. and Jabrane-Ferrat, N. and Marz, M. and Jung, J. U. and Sklan, E. H.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31142663},
doi = {10.1128/JVI.00211-19},
issn = {1098-5514 (Electronic) 0022-538X (Linking)},
year = {2019},
date = {2019-01-01},
journal = {J Virol},
volume = {93},
number = {16},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Brilland, Benoit; Beauvillain, Céline; Mazurkiewicz, Gery; Rucay, Pierre; Roquelaure, Yves; Tabiasco, Julie; Vinatier, Emeline; Riou, Jérémie; Jeannin, Pascale; Renier, Gilles; Subra, Jean-François; Augusto, Jean-François T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown Journal Article In: Frontiers in Immunology, vol. 10, pp. 2743, 2019, ISSN: 1664-3224. @article{brilland_t_2019,
title = {T Cell Dysregulation in Non-silicotic Silica Exposed Workers: A Step Toward Immune Tolerance Breakdown},
author = {Brilland, Benoit and Beauvillain, Céline and Mazurkiewicz, Gery and Rucay, Pierre and Roquelaure, Yves and Tabiasco, Julie and Vinatier, Emeline and Riou, Jérémie and Jeannin, Pascale and Renier, Gilles and Subra, Jean-François and Augusto, Jean-François},
doi = {10.3389/fimmu.2019.02743},
issn = {1664-3224},
year = {2019},
date = {2019-01-01},
journal = {Frontiers in Immunology},
volume = {10},
pages = {2743},
abstract = {Background: Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS. Methods: Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively. Results: Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for textless5 years, 18 for 5-10 years and 27 for more than 10 years. The frequency of Tregs (CD4+CD25+CD127-FoxP3+) was significantly lower in CS exposed workers as compared to HC. We found an increased expression of the activation marker HLA-DR on T cells (CD3+, CD4+, and CD8+) of CS exposed workers as compared to HC. Tregs to activated T cells ratio was also lower in exposed subjects. In the latter, HLA-DR expression level and Tregs frequency were significantly associated with CS exposure duration. Serum autoantibody detection was significantly higher in CS exposed workers as compared to HC. Especially, among workers exposed more than 10 years, antinuclear antibodies and ANCA were detected in 44 and 22% among them, as compared to 5 and 2.5% in HC, respectively. Conclusion: This work shows that CS exposure is associated with a decrease of Tregs frequency, an increase of T cell activation status, and a tolerance breakdown against auto-antigens. These results show that alterations of the T cell compartment can be detected early over the course of CS exposure, preceding silicosis development or AID onset.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Chronic silica exposure can lead to silicosis, complicated or not by autoimmune diseases (AID). The pathophysiology of silica-induced AID remains not fully understood, especially immune mechanisms that may develop in patients without yet established silicosis. We conducted a prospective clinical study to analyze the impact of crystalline silica (CS) on T cell phenotype and regulatory T cells (Tregs) frequency, as well as on auto-antibodies development in non-silicotic workers exposed to CS. Methods: Workers with moderate to high exposure level to CS and aged between 30 and 60 years-old were considered for inclusion. Peripheral blood mononuclear cells were analyzed by flow cytometry. Auto-antibodies were screened in serum by immunofluorescence. Blood from 42 and 45 healthy subjects (HC) was used as control for T cell phenotype and serum analyses, respectively. Results: Among the 63 included workers exposed to CS, 55 had full data available and were analyzed. Ten were exposed to CS for textless5 years, 18 for 5-10 years and 27 for more than 10 years. The frequency of Tregs (CD4+CD25+CD127-FoxP3+) was significantly lower in CS exposed workers as compared to HC. We found an increased expression of the activation marker HLA-DR on T cells (CD3+, CD4+, and CD8+) of CS exposed workers as compared to HC. Tregs to activated T cells ratio was also lower in exposed subjects. In the latter, HLA-DR expression level and Tregs frequency were significantly associated with CS exposure duration. Serum autoantibody detection was significantly higher in CS exposed workers as compared to HC. Especially, among workers exposed more than 10 years, antinuclear antibodies and ANCA were detected in 44 and 22% among them, as compared to 5 and 2.5% in HC, respectively. Conclusion: This work shows that CS exposure is associated with a decrease of Tregs frequency, an increase of T cell activation status, and a tolerance breakdown against auto-antigens. These results show that alterations of the T cell compartment can be detected early over the course of CS exposure, preceding silicosis development or AID onset. |
Alameddine, Joudy; Godefroy, Emmanuelle; Papargyris, Loukas; Sarrabayrouse, Guillaume; Tabiasco, Julie; Bridonneau, Chantal; Yazdanbakhsh, Karina; Sokol, Harry; Altare, Frédéric; Jotereau, Francine Faecalibacterium prausnitzii Skews Human DC to Prime IL10-Producing Ŧ Cells Through TLR2/6/JNK Signaling and IL-10, IL-27, CD39, and IDO-1 Induction Journal Article In: Frontiers in Immunology, vol. 10, pp. 143, 2019, ISSN: 1664-3224. @article{alameddine_faecalibacterium_2019,
title = {Faecalibacterium prausnitzii Skews Human DC to Prime IL10-Producing Ŧ Cells Through TLR2/6/JNK Signaling and IL-10, IL-27, CD39, and IDO-1 Induction},
author = {Alameddine, Joudy and Godefroy, Emmanuelle and Papargyris, Loukas and Sarrabayrouse, Guillaume and Tabiasco, Julie and Bridonneau, Chantal and Yazdanbakhsh, Karina and Sokol, Harry and Altare, Frédéric and Jotereau, Francine},
doi = {10.3389/fimmu.2019.00143},
issn = {1664-3224},
year = {2019},
date = {2019-01-01},
journal = {Frontiers in Immunology},
volume = {10},
pages = {143},
abstract = {The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The human colonic mucosa contains regulatory type 1-like (Tr1-like, i.e., IL-10-secreting and Foxp3-negative) T cells specific for the gut Clostridium Faecalibacterium prausnitzii (F. prausnitzii), which are both decreased in Crohn's disease patients. These data, together with the demonstration, in mice, that colonic regulatory T cells (Treg) induced by Clostridium bacteria are key players in colon homeostasis, support a similar role for F. prausnitzii-specific Treg in the human colon. Here we assessed the mechanisms whereby F. prausnitzii induces human colonic Treg. We demonstrated that F. prausnitzii, but not related Clostridia, skewed human dendritic cells to prime IL-10-secreting T cells. Accordingly, F. prausnitzii induced dendritic cells to express a unique array of potent Tr1/Treg polarizing molecules: IL-10, IL-27, CD39, IDO-1, and PDL-1 and, following TLR4 stimulation, inhibited their up-regulation of costimulation molecules as well as their production of pro-inflammatory cytokines IL-12 (p35 and p40) and TNFα. We further showed that these potent tolerogenic effects relied on F. prausnitzii-induced TLR2/6 triggering, JNK signaling and CD39 ectonucleotidase activity, which was induced by IDO-1 and IL-27. These data, together with the presence of F. prausnitzii-specific Tr1-like Treg in the human colon, point out to dendritic cells polarization by F. prausnitzii as the first described cellular mechanism whereby the microbiota composition may affect human colon homeostasis. Identification of F. prausnitzii-induced mediators involved in Tr1-like Treg induction by dendritic cells opens therapeutic avenues for the treatment of inflammatory bowel diseases. |
Mzoughi, O.; Teixido, M.; Planes, R.; Serrero, M.; Hamimed, I.; Zurita, E.; Moreno, M.; Granados, G.; Lakhdar-Ghazal, F.; BenMohamed, L.; Giralt, E.; Bahraoui, E. Trimeric Heptad Repeat Synthetic Peptides HR1 and HR2 Efficiently Inhibit HIV-1 Entry Journal Article In: Biosci Rep, 2019, ISSN: 1573-4935 (Electronic)
0144-8463 (Linking). @article{RN2699,
title = {Trimeric Heptad Repeat Synthetic Peptides HR1 and HR2 Efficiently Inhibit HIV-1 Entry},
author = {Mzoughi, O. and Teixido, M. and Planes, R. and Serrero, M. and Hamimed, I. and Zurita, E. and Moreno, M. and Granados, G. and Lakhdar-Ghazal, F. and BenMohamed, L. and Giralt, E. and Bahraoui, E.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31477581},
doi = {10.1042/BSR20192196},
issn = {1573-4935 (Electronic)
0144-8463 (Linking)},
year = {2019},
date = {2019-01-01},
journal = {Biosci Rep},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Hocine, H. R.; Brunel, S.; Chen, Q.; Giustiniani, J.; San Roman, M. J.; Ferrat, Y. J.; Palacios, I.; de la Rosa, O.; Lombardo, E.; Bensussan, A.; Charron, D.; Jabrane-Ferrat, N.; Al-Daccak, R. Extracellular Vesicles Released by Allogeneic Human Cardiac Stem/Progenitor Cells as Part of Their Therapeutic Benefit Journal Article In: Stem Cells Transl Med, vol. 8, no. 9, pp. 911-924, 2019, ISSN: 2157-6580 (Electronic)
2157-6564 (Linking). @article{RN2694,
title = {Extracellular Vesicles Released by Allogeneic Human Cardiac Stem/Progenitor Cells as Part of Their Therapeutic Benefit},
author = {Hocine, H. R. and Brunel, S. and Chen, Q. and Giustiniani, J. and San Roman, M. J. and Ferrat, Y. J. and Palacios, I. and de la Rosa, O. and Lombardo, E. and Bensussan, A. and Charron, D. and Jabrane-Ferrat, N. and Al-Daccak, R.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30924311},
doi = {10.1002/sctm.18-0256},
issn = {2157-6580 (Electronic)
2157-6564 (Linking)},
year = {2019},
date = {2019-01-01},
journal = {Stem Cells Transl Med},
volume = {8},
number = {9},
pages = {911-924},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Jabrane-Ferrat, N. Features of Human Decidual NK Cells in Healthy Pregnancy and During Viral Infection Journal Article In: Front Immunol, vol. 10, pp. 1397, 2019, ISSN: 1664-3224 (Electronic)
1664-3224 (Linking). @article{RN2692,
title = {Features of Human Decidual NK Cells in Healthy Pregnancy and During Viral Infection},
author = {Jabrane-Ferrat, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/31379803},
doi = {10.3389/fimmu.2019.01397},
issn = {1664-3224 (Electronic)
1664-3224 (Linking)},
year = {2019},
date = {2019-01-01},
journal = {Front Immunol},
volume = {10},
pages = {1397},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Mansuy, J. M.; El Costa, H.; Gouilly, J.; Mengelle, C.; Pasquier, C.; Martin-Blondel, G.; Izopet, J.; Jabrane-Ferrat, N. Peripheral Plasma and Semen Cytokine Response to Zika Virus in Humans Journal Article In: Emerg Infect Dis, vol. 25, no. 4, pp. 823-825, 2019, ISSN: 1080-6059 (Electronic)
1080-6040 (Linking). @article{RN2680,
title = {Peripheral Plasma and Semen Cytokine Response to Zika Virus in Humans},
author = {Mansuy, J. M. and El Costa, H. and Gouilly, J. and Mengelle, C. and Pasquier, C. and Martin-Blondel, G. and Izopet, J. and Jabrane-Ferrat, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30882325},
doi = {10.3201/eid2504.171886},
issn = {1080-6059 (Electronic)
1080-6040 (Linking)},
year = {2019},
date = {2019-01-01},
journal = {Emerg Infect Dis},
volume = {25},
number = {4},
pages = {823-825},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2018
|
Drouin, Olivier; Boutin, Amélie; Paquette, Kim; Gasse, Cédric; Guerby, Paul; Demers, Suzanne; Bujold, Emmanuel First-Trimester Uterine Artery Doppler for the Prediction of SGA at Birth: The Great Obstetrical Syndromes Study Journal Article In: Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC, vol. 40, no. 12, pp. 1592–1599, 2018, ISSN: 1701-2163. @article{drouin_first-trimester_2018,
title = {First-Trimester Uterine Artery Doppler for the Prediction of SGA at Birth: The Great Obstetrical Syndromes Study},
author = {Drouin, Olivier and Boutin, Amélie and Paquette, Kim and Gasse, Cédric and Guerby, Paul and Demers, Suzanne and Bujold, Emmanuel},
doi = {10.1016/j.jogc.2018.02.004},
issn = {1701-2163},
year = {2018},
date = {2018-12-01},
journal = {Journal of obstetrics and gynaecology Canada: JOGC = Journal d'obstetrique et gynecologie du Canada: JOGC},
volume = {40},
number = {12},
pages = {1592--1599},
abstract = {OBJECTIVE: To estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA).
METHODS: We conducted a prospective cohort study of nulliparous women with singleton pregnancy (Great Obstetrical Syndromes study). UtA-PI was performed at 11 + 0 to 13 + 6 weeks and was reported in multiple of median (MoM). SGA was defined as birth weight below the 10th percentile and stratified as term or preterm SGA. Receiver operating characteristic curves analyses with their area under the curve (AUC) were used to estimate the predictive values of UtA-PI, alone and UtA-PI combined with maternal characteristics. We computed the detection rate and false-positive rate (FPR) of the SOGC SGA screening guidelines in our population.
RESULTS: Of 4610 participants, SGA was identified in 486 pregnancies (10.3%), including 15 (0.3%) associated with preterm delivery. Compared with unaffected pregnancies, the mean log UtA-PI was significantly higher in term SGA and preterm SGA. The difference between preterm SGA and unaffected pregnancies remains significant after exclusion of SGA without preeclampsia. First-trimester UtA-PI was more predictive of preterm (AUC: 0.89) than term (AUC: 0.60) SGA (P textless 0.01). Combined with maternal characteristics, UtA-PI could have predicted 64% of preterm and 20% of term SGA (10% FPR). The SOGC guidelines criteria for early screening of SGA had a detection rate of 21% for a FPR of 21%.
CONCLUSIONS: First-trimester UtA-PI can be used to predict SGA, but mainly preterm SGA. The current SOGC guidelines criteria for SGA screening are not efficient in nulliparous women.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: To estimate the role of first-trimester uterine artery pulsatility index (UtA-PI) for the prediction of small-for-gestational age (SGA).
METHODS: We conducted a prospective cohort study of nulliparous women with singleton pregnancy (Great Obstetrical Syndromes study). UtA-PI was performed at 11 + 0 to 13 + 6 weeks and was reported in multiple of median (MoM). SGA was defined as birth weight below the 10th percentile and stratified as term or preterm SGA. Receiver operating characteristic curves analyses with their area under the curve (AUC) were used to estimate the predictive values of UtA-PI, alone and UtA-PI combined with maternal characteristics. We computed the detection rate and false-positive rate (FPR) of the SOGC SGA screening guidelines in our population.
RESULTS: Of 4610 participants, SGA was identified in 486 pregnancies (10.3%), including 15 (0.3%) associated with preterm delivery. Compared with unaffected pregnancies, the mean log UtA-PI was significantly higher in term SGA and preterm SGA. The difference between preterm SGA and unaffected pregnancies remains significant after exclusion of SGA without preeclampsia. First-trimester UtA-PI was more predictive of preterm (AUC: 0.89) than term (AUC: 0.60) SGA (P textless 0.01). Combined with maternal characteristics, UtA-PI could have predicted 64% of preterm and 20% of term SGA (10% FPR). The SOGC guidelines criteria for early screening of SGA had a detection rate of 21% for a FPR of 21%.
CONCLUSIONS: First-trimester UtA-PI can be used to predict SGA, but mainly preterm SGA. The current SOGC guidelines criteria for SGA screening are not efficient in nulliparous women. |
Gouilly, J.; Chen, Q.; Siewiera, J.; Cartron, G.; Levy, C.; Dubois, M.; Al-Daccak, R.; Izopet, J.; Jabrane-Ferrat, N.; El Costa, H. Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface Journal Article In: Nat Commun, vol. 9, no. 1, pp. 4748, 2018, ISSN: 2041-1723 (Electronic) 2041-1723 (Linking). @article{RN861,
title = {Genotype specific pathogenicity of hepatitis E virus at the human maternal-fetal interface},
author = {Gouilly, J. and Chen, Q. and Siewiera, J. and Cartron, G. and Levy, C. and Dubois, M. and Al-Daccak, R. and Izopet, J. and Jabrane-Ferrat, N. and El Costa, H.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30420629},
doi = {10.1038/s41467-018-07200-2},
issn = {2041-1723 (Electronic) 2041-1723 (Linking)},
year = {2018},
date = {2018-01-01},
journal = {Nat Commun},
volume = {9},
number = {1},
pages = {4748},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Planes, R.; Serrero, M.; Leghmari, K.; BenMohamed, L.; Bahraoui, E. HIV-1 Envelope Glycoproteins Induce the Production of TNF-alpha and IL-10 in Human Monocytes by Activating Calcium Pathway Journal Article In: Sci Rep, vol. 8, no. 1, pp. 17215, 2018, ISSN: 2045-2322 (Electronic)
2045-2322 (Linking). @article{RN868,
title = {HIV-1 Envelope Glycoproteins Induce the Production of TNF-alpha and IL-10 in Human Monocytes by Activating Calcium Pathway},
author = {Planes, R. and Serrero, M. and Leghmari, K. and BenMohamed, L. and Bahraoui, E.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/30464243},
doi = {10.1038/s41598-018-35478-1},
issn = {2045-2322 (Electronic)
2045-2322 (Linking)},
year = {2018},
date = {2018-01-01},
journal = {Sci Rep},
volume = {8},
number = {1},
pages = {17215},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Srivastava, R.; Hernandez-Ruiz, M.; Khan, A. A.; Fouladi, M. A.; Kim, G. J.; Ly, V. T.; Yamada, T.; Lam, C.; Sarain, S. A. B.; Boldbaatar, U.; Zlotnik, A.; Bahraoui, E.; BenMohamed, L. CXCL17 Chemokine-Dependent Mobilization of CXCR8(+)CD8(+) Effector Memory and Tissue-Resident Memory T Cells in the Vaginal Mucosa Is Associated with Protection against Genital Herpes Journal Article In: J Immunol, vol. 200, no. 8, pp. 2915-2926, 2018, ISSN: 1550-6606 (Electronic)
0022-1767 (Linking). @article{RN869,
title = {CXCL17 Chemokine-Dependent Mobilization of CXCR8(+)CD8(+) Effector Memory and Tissue-Resident Memory T Cells in the Vaginal Mucosa Is Associated with Protection against Genital Herpes},
author = {Srivastava, R. and Hernandez-Ruiz, M. and Khan, A. A. and Fouladi, M. A. and Kim, G. J. and Ly, V. T. and Yamada, T. and Lam, C. and Sarain, S. A. B. and Boldbaatar, U. and Zlotnik, A. and Bahraoui, E. and BenMohamed, L.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/29549178},
doi = {10.4049/jimmunol.1701474},
issn = {1550-6606 (Electronic)
0022-1767 (Linking)},
year = {2018},
date = {2018-01-01},
journal = {J Immunol},
volume = {200},
number = {8},
pages = {2915-2926},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Lopes, P. P.; Todorov, G.; Pham, T. T.; Nesburn, A. B.; Bahraoui, E.; BenMohamed, L. Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8(+) TEM and TRM Cell Responses against Herpesvirus Infection and Disease Journal Article In: J Virol, vol. 92, no. 8, 2018, ISSN: 1098-5514 (Electronic)
0022-538X (Linking). @article{RN870,
title = {Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8(+) TEM and TRM Cell Responses against Herpesvirus Infection and Disease},
author = {Lopes, P. P. and Todorov, G. and Pham, T. T. and Nesburn, A. B. and Bahraoui, E. and BenMohamed, L.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/29437976},
doi = {10.1128/JVI.02156-17},
issn = {1098-5514 (Electronic)
0022-538X (Linking)},
year = {2018},
date = {2018-01-01},
journal = {J Virol},
volume = {92},
number = {8},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Roy, Charlotte; Tabiasco, Julie; Caillon, Antoine; Delneste, Yves; Merot, Jean; Favre, Julie; Guihot, Anne Laure; Martin, Ludovic; Nascimento, Daniele C.; Ryffel, Bernhard; Robson, Simon C.; Sévigny, Jean; Henrion, Daniel; Kauffenstein, Gilles Loss of vascular expression of nucleoside triphosphate diphosphohydrolase-1/CD39 in hypertension Journal Article In: Purinergic Signalling, vol. 14, no. 1, pp. 73–82, 2018, ISSN: 1573-9546. @article{roy_loss_2018,
title = {Loss of vascular expression of nucleoside triphosphate diphosphohydrolase-1/CD39 in hypertension},
author = {Roy, Charlotte and Tabiasco, Julie and Caillon, Antoine and Delneste, Yves and Merot, Jean and Favre, Julie and Guihot, Anne Laure and Martin, Ludovic and Nascimento, Daniele C. and Ryffel, Bernhard and Robson, Simon C. and Sévigny, Jean and Henrion, Daniel and Kauffenstein, Gilles},
doi = {10.1007/s11302-017-9597-9},
issn = {1573-9546},
year = {2018},
date = {2018-01-01},
journal = {Purinergic Signalling},
volume = {14},
number = {1},
pages = {73--82},
abstract = {Ectonucleoside triphosphate diphosphohydrolase-1, the major vascular/immune ectonucleotidase, exerts anti-thrombotic and immunomodulatory actions by hydrolyzing extracellular nucleotides (danger signals). Hypertension is characterized by vascular wall remodeling, endothelial dysfunction, and immune infiltration. Here our aim was to investigate the impact of arterial hypertension on CD39 expression and activity in mice. Arterial expression of CD39 was determined by reverse transcription quantitative real-time PCR in experimental models of hypertension, including angiotensin II (AngII)-treated mice (1 mg/kg/day, 21 days), deoxycorticosterone acetate-salt mice (1% salt and uninephrectomy, 21 days), and spontaneously hypertensive rats. A decrease in CD39 expression occurred in the resistance and conductance arteries of hypertensive animals with no effect on lymphoid organs. In AngII-treated mice, a decrease in CD39 protein levels (Western blot) was corroborated by reduced arterial nucleotidase activity, as evaluated by fluorescent (etheno)-ADP hydrolysis. Moreover, serum-soluble ADPase activity, supported by CD39, was significantly decreased in AngII-treated mice. Experiments were conducted in vitro on vascular cells to determine the elements underlying this downregulation. We found that CD39 transcription was reduced by proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor alpha on vascular smooth muscle cells and by IL-6 and anti-inflammatory and profibrotic cytokine transforming growth factor beta 1 on endothelial cells. In addition, CD39 expression was downregulated by mechanical stretch on vascular cells. Arterial expression and activity of CD39 were decreased in hypertension as a result of both a proinflammatory environment and mechanical strain exerted on vascular cells. Reduced ectonucleotidase activity may alter the vascular condition, thus enhancing arterial damage, remodeling, or thrombotic events.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ectonucleoside triphosphate diphosphohydrolase-1, the major vascular/immune ectonucleotidase, exerts anti-thrombotic and immunomodulatory actions by hydrolyzing extracellular nucleotides (danger signals). Hypertension is characterized by vascular wall remodeling, endothelial dysfunction, and immune infiltration. Here our aim was to investigate the impact of arterial hypertension on CD39 expression and activity in mice. Arterial expression of CD39 was determined by reverse transcription quantitative real-time PCR in experimental models of hypertension, including angiotensin II (AngII)-treated mice (1 mg/kg/day, 21 days), deoxycorticosterone acetate-salt mice (1% salt and uninephrectomy, 21 days), and spontaneously hypertensive rats. A decrease in CD39 expression occurred in the resistance and conductance arteries of hypertensive animals with no effect on lymphoid organs. In AngII-treated mice, a decrease in CD39 protein levels (Western blot) was corroborated by reduced arterial nucleotidase activity, as evaluated by fluorescent (etheno)-ADP hydrolysis. Moreover, serum-soluble ADPase activity, supported by CD39, was significantly decreased in AngII-treated mice. Experiments were conducted in vitro on vascular cells to determine the elements underlying this downregulation. We found that CD39 transcription was reduced by proinflammatory cytokines interleukin (IL)-1β and tumor necrosis factor alpha on vascular smooth muscle cells and by IL-6 and anti-inflammatory and profibrotic cytokine transforming growth factor beta 1 on endothelial cells. In addition, CD39 expression was downregulated by mechanical stretch on vascular cells. Arterial expression and activity of CD39 were decreased in hypertension as a result of both a proinflammatory environment and mechanical strain exerted on vascular cells. Reduced ectonucleotidase activity may alter the vascular condition, thus enhancing arterial damage, remodeling, or thrombotic events. |
2017
|
Hocine, H. R.; Costa, H. E.; Dam, N.; Giustiniani, J.; Palacios, I.; Loiseau, P.; Bensussan, A.; Borlado, L. R.; Charron, D.; Suberbielle, C.; Jabrane-Ferrat, N.; Al-Daccak, R. Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells Journal Article In: Sci Rep, vol. 7, pp. 41125, 2017, ISSN: 2045-2322 (Electronic)
2045-2322 (Linking). @article{RN863,
title = {Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells},
author = {Hocine, H. R. and Costa, H. E. and Dam, N. and Giustiniani, J. and Palacios, I. and Loiseau, P. and Bensussan, A. and Borlado, L. R. and Charron, D. and Suberbielle, C. and Jabrane-Ferrat, N. and Al-Daccak, R.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28117403},
doi = {10.1038/srep41125},
issn = {2045-2322 (Electronic)
2045-2322 (Linking)},
year = {2017},
date = {2017-01-01},
journal = {Sci Rep},
volume = {7},
pages = {41125},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Dam, N.; Hocine, H. R.; Palacios, I.; DelaRosa, O.; Menta, R.; Charron, D.; Bensussan, A.; El Costa, H.; Jabrane-Ferrat, N.; Dalemans, W.; Lombardo, E.; Al-Daccak, R. Human Cardiac-Derived Stem/Progenitor Cells Fine-Tune Monocyte-Derived Descendants Activities toward Cardiac Repair Journal Article In: Front Immunol, vol. 8, pp. 1413, 2017, ISSN: 1664-3224 (Print)
1664-3224 (Linking). @article{RN862,
title = {Human Cardiac-Derived Stem/Progenitor Cells Fine-Tune Monocyte-Derived Descendants Activities toward Cardiac Repair},
author = {Dam, N. and Hocine, H. R. and Palacios, I. and DelaRosa, O. and Menta, R. and Charron, D. and Bensussan, A. and El Costa, H. and Jabrane-Ferrat, N. and Dalemans, W. and Lombardo, E. and Al-Daccak, R.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/29123530},
doi = {10.3389/fimmu.2017.01413},
issn = {1664-3224 (Print)
1664-3224 (Linking)},
year = {2017},
date = {2017-01-01},
journal = {Front Immunol},
volume = {8},
pages = {1413},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Serrero, M.; Planes, R.; Bahraoui, E. PKC-delta isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-kappaB and CXCL8 production Journal Article In: Sci Rep, vol. 7, no. 1, pp. 2384, 2017, ISSN: 2045-2322 (Electronic)
2045-2322 (Linking). @article{RN871,
title = {PKC-delta isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-kappaB and CXCL8 production},
author = {Serrero, M. and Planes, R. and Bahraoui, E.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28539656},
doi = {10.1038/s41598-017-02468-8},
issn = {2045-2322 (Electronic)
2045-2322 (Linking)},
year = {2017},
date = {2017-01-01},
journal = {Sci Rep},
volume = {7},
number = {1},
pages = {2384},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Srivastava, R.; Khan, A. A.; Chilukuri, S.; Syed, S. A.; Tran, T. T.; Furness, J.; Bahraoui, E.; BenMohamed, L. CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8(+) TEM and CD8(+) TRM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease Journal Article In: J Virol, vol. 91, no. 14, 2017, ISSN: 1098-5514 (Electronic)
0022-538X (Linking). @article{RN872,
title = {CXCL10/CXCR3-Dependent Mobilization of Herpes Simplex Virus-Specific CD8(+) TEM and CD8(+) TRM Cells within Infected Tissues Allows Efficient Protection against Recurrent Herpesvirus Infection and Disease},
author = {Srivastava, R. and Khan, A. A. and Chilukuri, S. and Syed, S. A. and Tran, T. T. and Furness, J. and Bahraoui, E. and BenMohamed, L.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28468883},
doi = {10.1128/JVI.00278-17},
issn = {1098-5514 (Electronic)
0022-538X (Linking)},
year = {2017},
date = {2017-01-01},
journal = {J Virol},
volume = {91},
number = {14},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2016
|
d'Almeida, Sènan M.; Kauffenstein, Gilles; Roy, Charlotte; Basset, Laetitia; Papargyris, Loukas; Henrion, Daniel; Catros, Véronique; Ifrah, Norbert; Descamps, Philippe; Croue, Anne; Jeannin, Pascale; Grégoire, Marc; Delneste, Yves; Tabiasco, Julie The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27 Journal Article In: Oncoimmunology, vol. 5, no. 7, pp. e1178025, 2016, ISSN: 2162-4011. @article{dalmeida_ecto-atpdase_2016,
title = {The ecto-ATPDase CD39 is involved in the acquisition of the immunoregulatory phenotype by M-CSF-macrophages and ovarian cancer tumor-associated macrophages: Regulatory role of IL-27},
author = {d'Almeida, Sènan M. and Kauffenstein, Gilles and Roy, Charlotte and Basset, Laetitia and Papargyris, Loukas and Henrion, Daniel and Catros, Véronique and Ifrah, Norbert and Descamps, Philippe and Croue, Anne and Jeannin, Pascale and Grégoire, Marc and Delneste, Yves and Tabiasco, Julie},
doi = {10.1080/2162402X.2016.1178025},
issn = {2162-4011},
year = {2016},
date = {2016-01-01},
journal = {Oncoimmunology},
volume = {5},
number = {7},
pages = {e1178025},
abstract = {Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14(+) CD163(+) TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14(high) CD163(high) CD39(high) macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163(+) macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tumor-associated macrophages (TAM) are immunosuppressive cells that can massively accumulate in the tumor microenvironment. In patients with ovarian cancer, their density is correlated with poor prognosis. Targeting mediators that control the generation or the differentiation of immunoregulatory macrophages represents a therapeutic challenge to overcome tumor-associated immunosuppression. The ectonucleotidase CD39 hydrolyzes ATP into extracellular adenosine that exhibits potent immunosuppressive properties when signaling through the A2A adenosine receptor. We report here that CD14(+) CD163(+) TAM isolated from ovarian cancer patients and macrophages generated in vitro with M-CSF, express high levels of the membrane ectonucleotidase CD39 compared to classically activated macrophages. The CD39 inhibitor POM-1 and adenosine deaminase (ADA) diminished some of the immunosuppressive functions of CD14(high) CD163(high) CD39(high) macrophages, such as IL-10 secretion. We identified the cytokine IL-27, secreted by tumor-infiltrating neutrophils, located close to infiltrating CD163(+) macrophages, as a major rheostat of CD39 expression and consequently, on the acquisition of immunoregulatory properties by macrophages. Accordingly, the depletion of IL-27 downregulated CD39 and PD-L1 expression as well as IL-10 secretion by M-CSF-macrophages. Collectively, these data suggest that CD39, drived by IL-27 and CD115 ligands in ovarian cancer, maintains the immunosuppressive phenotype of TAM. This work brings new information on the acquisition of immunosuppressive properties by tumor-infiltrating macrophages. |
El Costa, H.; Gouilly, J.; Mansuy, J. M.; Chen, Q.; Levy, C.; Cartron, G.; Veas, F.; Al-Daccak, R.; Izopet, J.; Jabrane-Ferrat, N. ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy Journal Article In: Sci Rep, vol. 6, pp. 35296, 2016, ISSN: 2045-2322 (Electronic)
2045-2322 (Linking). @article{RN14b,
title = {ZIKA virus reveals broad tissue and cell tropism during the first trimester of pregnancy},
author = {El Costa, H. and Gouilly, J. and Mansuy, J. M. and Chen, Q. and Levy, C. and Cartron, G. and Veas, F. and Al-Daccak, R. and Izopet, J. and Jabrane-Ferrat, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27759009},
doi = {10.1038/srep35296},
issn = {2045-2322 (Electronic)
2045-2322 (Linking)},
year = {2016},
date = {2016-01-01},
journal = {Sci Rep},
volume = {6},
pages = {35296},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Vidal, Fabien; Guerby, Paul; Luyckx, Mathieu; Haddad, Pascale; Stoeckle, Eberhard; Morice, Philippe; Leblanc, Eric; Lecuru, Fabrice; Daraï, Emile; Classe, Jean Marc; Pomel, Christophe; Filleron, Thomas; Ferron, Gwenael; Querleu, Denis; Rafii, Arash Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis? Journal Article In: PloS One, vol. 11, no. 1, pp. e0147787, 2016, ISSN: 1932-6203. @article{vidal_are_2016,
title = {Are Early Relapses in Advanced-Stage Ovarian Cancer Doomed to a Poor Prognosis?},
author = {Vidal, Fabien and Guerby, Paul and Luyckx, Mathieu and Haddad, Pascale and Stoeckle, Eberhard and Morice, Philippe and Leblanc, Eric and Lecuru, Fabrice and Daraï, Emile and Classe, Jean Marc and Pomel, Christophe and Filleron, Thomas and Ferron, Gwenael and Querleu, Denis and Rafii, Arash},
doi = {10.1371/journal.pone.0147787},
issn = {1932-6203},
year = {2016},
date = {2016-01-01},
journal = {PloS One},
volume = {11},
number = {1},
pages = {e0147787},
abstract = {OBJECTIVE: Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.
STUDY DESIGN: We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. RESULTS: The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
OBJECTIVE: Early recurrence (ER) after completion of therapeutic regimen in advanced-stage ovarian cancer is a challenging clinical situation. Patients are perceived as invariably having a poor prognosis. We investigated the possibility of defining different prognostic subgroups and the parameters implicated in prognosis of ER patients.
STUDY DESIGN: We analyzed a multi-centric database of 527 FIGO stage IIIC and IV ovarian cancer patients. We defined patients relapsing within 12 months as ER and investigated using Cox logistic regression the prognostic factors in ER group. We subsequently divided ER patients into good and poor prognosis groups according to a lower or higher overall survival (OS) at 12 months after relapse and determined parameters associated to poor prognosis. RESULTS: The median follow up was 49 months. One hundred and thirty eight patients recurred within 12 months. OS and Disease Free Survival (DFS) were 24.6 and 8.6 months, respectively, in this group of patients. Among the ER patients, 73 had a poor prognosis with an OS after relapse below 12 months (mean OS = 5.2 months) and 65 survived after one year (mean OS = 26.9 months). Residual disease (RD) after debulking surgery and mucinous histological subtype negatively impacted prognosis (HR = 1.758 |
Planes, R.; Ben Haij, N.; Leghmari, K.; Serrero, M.; BenMohamed, L.; Bahraoui, E. HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways To Induce Tumor Necrosis Factor Alpha and Interleukin-10 in Human Monocytes Journal Article In: J Virol, vol. 90, no. 13, pp. 5886-5898, 2016, ISSN: 1098-5514 (Electronic)
0022-538X (Linking). @article{RN873,
title = {HIV-1 Tat Protein Activates both the MyD88 and TRIF Pathways To Induce Tumor Necrosis Factor Alpha and Interleukin-10 in Human Monocytes},
author = {Planes, R. and Ben Haij, N. and Leghmari, K. and Serrero, M. and BenMohamed, L. and Bahraoui, E.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27053552},
doi = {10.1128/JVI.00262-16},
issn = {1098-5514 (Electronic)
0022-538X (Linking)},
year = {2016},
date = {2016-01-01},
journal = {J Virol},
volume = {90},
number = {13},
pages = {5886-5898},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Chéné, Anne-Laure; d'Almeida, Sènan; Blondy, Thibaut; Tabiasco, Julie; Deshayes, Sophie; Fonteneau, Jean-François; Cellerin, Laurent; Delneste, Yves; Grégoire, Marc; Blanquart, Christophe Pleural Effusions from Patients with Mesothelioma Induce Recruitment of Monocytes and Their Differentiation into M2 Macrophages Journal Article In: Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer, vol. 11, no. 10, pp. 1765–1773, 2016, ISSN: 1556-1380. @article{chene_pleural_2016,
title = {Pleural Effusions from Patients with Mesothelioma Induce Recruitment of Monocytes and Their Differentiation into M2 Macrophages},
author = {Chéné, Anne-Laure and d'Almeida, Sènan and Blondy, Thibaut and Tabiasco, Julie and Deshayes, Sophie and Fonteneau, Jean-François and Cellerin, Laurent and Delneste, Yves and Grégoire, Marc and Blanquart, Christophe},
doi = {10.1016/j.jtho.2016.06.022},
issn = {1556-1380},
year = {2016},
date = {2016-01-01},
journal = {Journal of Thoracic Oncology: Official Publication of the International Association for the Study of Lung Cancer},
volume = {11},
number = {10},
pages = {1765--1773},
abstract = {INTRODUCTION: Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PEs) from patients with mesothelioma contain high levels of the C-C motif chemokine ligand 2 (CCL2) inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples, particularly on monocyte recruitment. Then, we studied the fate of these monocytes in malignant pleural mesothelioma (MPM) PEs and their impact on tumor cells' properties.
METHODS: The implication of CCL2 in monocyte recruitment was evaluated using transmigration assays and a CCL2 blocking antibody. The phenotype of macrophages was determined by flow cytometry and enzyme-linked immunosorbent assay. Immunohistochemical analysis was used to support the results. Cocultures of macrophages with mesothelioma cells were performed to study cancer cell proliferation and resistance to treatment.
RESULTS: We showed that CCL2 is a major factor of monocyte recruitment induced by MPM samples. Macrophages obtained in MPM samples were M2 macrophages (high CD14, high CD163, and interleukin-10 secretion after activation). The colony-stimulating factor 1 receptor/macrophage colony-stimulating factor (M-CSF) pathway is implicated in M2 polarization, and high levels of M-CSF were measured in MPM samples compared with benign PE (4.17 ± 2.75 ng/mL and 1.94 ± 1.47 ng/mL, respectively). Immunohistochemical analysis confirmed the presence of M2 macrophages in pleural and peritoneal mesothelioma. Finally, we showed that M2 macrophages increased mesothelioma cell proliferation and resistance to treatment.
CONCLUSIONS: These results demonstrate the implication of CCL2 in MPM pathogenesis and designate M-CSF as a new potential biomarker of MPM. This study also identifies CCL2 and colony-stimulating factor 1 receptor/M-CSF as interesting new targets to modulate pro-tumorigenic properties of the tumor microenvironment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
INTRODUCTION: Mesothelioma is a rare and aggressive cancer related to asbestos exposure. We recently showed that pleural effusions (PEs) from patients with mesothelioma contain high levels of the C-C motif chemokine ligand 2 (CCL2) inflammatory chemokine. In the present work, we studied the effect of CCL2 contained in mesothelioma samples, particularly on monocyte recruitment. Then, we studied the fate of these monocytes in malignant pleural mesothelioma (MPM) PEs and their impact on tumor cells' properties.
METHODS: The implication of CCL2 in monocyte recruitment was evaluated using transmigration assays and a CCL2 blocking antibody. The phenotype of macrophages was determined by flow cytometry and enzyme-linked immunosorbent assay. Immunohistochemical analysis was used to support the results. Cocultures of macrophages with mesothelioma cells were performed to study cancer cell proliferation and resistance to treatment.
RESULTS: We showed that CCL2 is a major factor of monocyte recruitment induced by MPM samples. Macrophages obtained in MPM samples were M2 macrophages (high CD14, high CD163, and interleukin-10 secretion after activation). The colony-stimulating factor 1 receptor/macrophage colony-stimulating factor (M-CSF) pathway is implicated in M2 polarization, and high levels of M-CSF were measured in MPM samples compared with benign PE (4.17 ± 2.75 ng/mL and 1.94 ± 1.47 ng/mL, respectively). Immunohistochemical analysis confirmed the presence of M2 macrophages in pleural and peritoneal mesothelioma. Finally, we showed that M2 macrophages increased mesothelioma cell proliferation and resistance to treatment.
CONCLUSIONS: These results demonstrate the implication of CCL2 in MPM pathogenesis and designate M-CSF as a new potential biomarker of MPM. This study also identifies CCL2 and colony-stimulating factor 1 receptor/M-CSF as interesting new targets to modulate pro-tumorigenic properties of the tumor microenvironment. |
2015
|
Ainaoui, N.; Hantelys, F.; Renaud-Gabardos, E.; Bunel, M.; Lopez, F.; Pujol, F.; Planes, R.; Bahraoui, E.; Pichereaux, C.; Burlet-Schiltz, O.; Parini, A.; Garmy-Susini, B.; Prats, A. C. Promoter-Dependent Translation Controlled by p54nrb and hnRNPM during Myoblast Differentiation Journal Article In: PLoS One, vol. 10, no. 9, pp. e0136466, 2015, ISSN: 1932-6203 (Electronic)
1932-6203 (Linking). @article{RN874,
title = {Promoter-Dependent Translation Controlled by p54nrb and hnRNPM during Myoblast Differentiation},
author = {Ainaoui, N. and Hantelys, F. and Renaud-Gabardos, E. and Bunel, M. and Lopez, F. and Pujol, F. and Planes, R. and Bahraoui, E. and Pichereaux, C. and Burlet-Schiltz, O. and Parini, A. and Garmy-Susini, B. and Prats, A. C.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26332123},
doi = {10.1371/journal.pone.0136466},
issn = {1932-6203 (Electronic)
1932-6203 (Linking)},
year = {2015},
date = {2015-01-01},
journal = {PLoS One},
volume = {10},
number = {9},
pages = {e0136466},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Siewiera, J.; Gouilly, J.; Hocine, H. R.; Cartron, G.; Levy, C.; Al-Daccak, R.; Jabrane-Ferrat, N. Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell subtypes Journal Article In: Nat Commun, vol. 6, pp. 10183, 2015, ISSN: 2041-1723 (Electronic)
2041-1723 (Linking). @article{RN864,
title = {Natural cytotoxicity receptor splice variants orchestrate the distinct functions of human natural killer cell subtypes},
author = {Siewiera, J. and Gouilly, J. and Hocine, H. R. and Cartron, G. and Levy, C. and Al-Daccak, R. and Jabrane-Ferrat, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26666685},
doi = {10.1038/ncomms10183},
issn = {2041-1723 (Electronic)
2041-1723 (Linking)},
year = {2015},
date = {2015-01-01},
journal = {Nat Commun},
volume = {6},
pages = {10183},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Mina, Sara; Staerck, Cindy; d'Almeida, Sènan M.; Marot, Agnès; Delneste, Yves; Calenda, Alphonse; Tabiasco, Julie; Bouchara, Jean-Philippe; Fleury, Maxime J. J. Identification of Scedosporium boydii catalase A1 gene, a reactive oxygen species detoxification factor highly expressed in response to oxidative stress and phagocytic cells Journal Article In: Fungal Biology, vol. 119, no. 12, pp. 1322–1333, 2015, ISSN: 1878-6146. @article{mina_identification_2015,
title = {Identification of Scedosporium boydii catalase A1 gene, a reactive oxygen species detoxification factor highly expressed in response to oxidative stress and phagocytic cells},
author = {Mina, Sara and Staerck, Cindy and d'Almeida, Sènan M. and Marot, Agnès and Delneste, Yves and Calenda, Alphonse and Tabiasco, Julie and Bouchara, Jean-Philippe and Fleury, Maxime J. J.},
doi = {10.1016/j.funbio.2015.09.007},
issn = {1878-6146},
year = {2015},
date = {2015-01-01},
journal = {Fungal Biology},
volume = {119},
number = {12},
pages = {1322--1333},
abstract = {Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a large variety of infections in both immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Species of the S. apiospermum complex are able to chronically colonize the CF airways suggesting pathogenic mechanisms allowing persistence and growth of these fungi in the respiratory tract. Few putative virulence factors have been purified and characterized so far in the S. apiospermum complex including a cytosolic Cu,Zn-superoxide dismutase (SOD) and a monofunctional catalase (catalase A1). Upon microbial infection, host phagocytes release reactive oxygen species (ROS), such as hydrogen peroxide, as part of the antimicrobial response. Catalases are known to protect pathogens against ROS by degradation of the hydrogen peroxide. Here, we identified the S. boydii catalase A1 gene (CATA1) and investigated its expression in response to the environmental conditions encountered in the CF airways and to the oxidative stress. Results showed that S. boydii CATA1 gene expression is not affected by hypoxia, hypercapnia or pH changes. In contrast, CATA1 gene was overexpressed in response to a chemically induced oxidative stress with a relative gene expression 37-fold higher in the presence of 250 μM H(2)O(2), 20-fold higher with 250 μM menadione and 5-fold higher with 2 mM paraquat. Moreover, S. boydii CATA1 gene expression progressively increased upon exposure to activated THP-1-derived macrophages, reaching a maximum after 12 h (26 fold). Activated HL60-derived neutrophils and activated human peripheral blood neutrophils more rapidly induced S. boydii CATA1 gene overexpression, a maximum gene expression level being reached at 75 min (17 fold) and 60 min (15 fold), respectively. In contrast expression of the gene encoding the Cu,Zn-SOD (SODC gene) was not affected by H(2)O(2), menadione, paraquat or in co-culture with phagocytic cells. These results suggest that S. boydii CATA1 gene is highly stimulated by the oxidative burst response whereas SODC gene is constitutively expressed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Scedosporium boydii is an opportunistic filamentous fungus which may be responsible for a large variety of infections in both immunocompetent and immunocompromised individuals. This fungus belongs to the Scedosporium apiospermum species complex which usually ranks second among the filamentous fungi colonizing the airways of patients with cystic fibrosis (CF). Species of the S. apiospermum complex are able to chronically colonize the CF airways suggesting pathogenic mechanisms allowing persistence and growth of these fungi in the respiratory tract. Few putative virulence factors have been purified and characterized so far in the S. apiospermum complex including a cytosolic Cu,Zn-superoxide dismutase (SOD) and a monofunctional catalase (catalase A1). Upon microbial infection, host phagocytes release reactive oxygen species (ROS), such as hydrogen peroxide, as part of the antimicrobial response. Catalases are known to protect pathogens against ROS by degradation of the hydrogen peroxide. Here, we identified the S. boydii catalase A1 gene (CATA1) and investigated its expression in response to the environmental conditions encountered in the CF airways and to the oxidative stress. Results showed that S. boydii CATA1 gene expression is not affected by hypoxia, hypercapnia or pH changes. In contrast, CATA1 gene was overexpressed in response to a chemically induced oxidative stress with a relative gene expression 37-fold higher in the presence of 250 μM H(2)O(2), 20-fold higher with 250 μM menadione and 5-fold higher with 2 mM paraquat. Moreover, S. boydii CATA1 gene expression progressively increased upon exposure to activated THP-1-derived macrophages, reaching a maximum after 12 h (26 fold). Activated HL60-derived neutrophils and activated human peripheral blood neutrophils more rapidly induced S. boydii CATA1 gene overexpression, a maximum gene expression level being reached at 75 min (17 fold) and 60 min (15 fold), respectively. In contrast expression of the gene encoding the Cu,Zn-SOD (SODC gene) was not affected by H(2)O(2), menadione, paraquat or in co-culture with phagocytic cells. These results suggest that S. boydii CATA1 gene is highly stimulated by the oxidative burst response whereas SODC gene is constitutively expressed. |
Ben Haij, N.; Planes, R.; Leghmari, K.; Serrero, M.; Delobel, P.; Izopet, J.; BenMohamed, L.; Bahraoui, E. HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-kappaB Pathway Journal Article In: PLoS One, vol. 10, no. 6, pp. e0129425, 2015, ISSN: 1932-6203 (Electronic)
1932-6203 (Linking). @article{RN875,
title = {HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-kappaB Pathway},
author = {Ben Haij, N. and Planes, R. and Leghmari, K. and Serrero, M. and Delobel, P. and Izopet, J. and BenMohamed, L. and Bahraoui, E.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26090662},
doi = {10.1371/journal.pone.0129425},
issn = {1932-6203 (Electronic)
1932-6203 (Linking)},
year = {2015},
date = {2015-01-01},
journal = {PLoS One},
volume = {10},
number = {6},
pages = {e0129425},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
2014
|
Planes, R.; BenMohamed, L.; Leghmari, K.; Delobel, P.; Izopet, J.; Bahraoui, E. HIV-1 Tat protein induces PD-L1 (B7-H1) expression on dendritic cells through tumor necrosis factor alpha- and toll-like receptor 4-mediated mechanisms Journal Article In: J Virol, vol. 88, no. 12, pp. 6672-89, 2014, ISSN: 1098-5514 (Electronic)
0022-538X (Linking). @article{RN877,
title = {HIV-1 Tat protein induces PD-L1 (B7-H1) expression on dendritic cells through tumor necrosis factor alpha- and toll-like receptor 4-mediated mechanisms},
author = {Planes, R. and BenMohamed, L. and Leghmari, K. and Delobel, P. and Izopet, J. and Bahraoui, E.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24696476},
doi = {10.1128/JVI.00825-14},
issn = {1098-5514 (Electronic)
0022-538X (Linking)},
year = {2014},
date = {2014-01-01},
journal = {J Virol},
volume = {88},
number = {12},
pages = {6672-89},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Jabrane-Ferrat, N.; Siewiera, J. The up side of decidual natural killer cells: new developments in immunology of pregnancy Journal Article In: Immunology, vol. 141, no. 4, pp. 490-7, 2014, ISSN: 1365-2567 (Electronic)
0019-2805 (Linking). @article{RN867,
title = {The up side of decidual natural killer cells: new developments in immunology of pregnancy},
author = {Jabrane-Ferrat, N. and Siewiera, J.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24256296},
doi = {10.1111/imm.12218},
issn = {1365-2567 (Electronic)
0019-2805 (Linking)},
year = {2014},
date = {2014-01-01},
journal = {Immunology},
volume = {141},
number = {4},
pages = {490-7},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Lauden, L.; Siewiera, J.; Boukouaci, W.; Ramgolam, K.; Mourah, S.; Lebbe, C.; Charron, D.; Aoudjit, F.; Jabrane-Ferrat, N.; Al-Daccak, R. TGF-beta-induced (TGFBI) protein in melanoma: a signature of high metastatic potential Journal Article In: J Invest Dermatol, vol. 134, no. 6, pp. 1675-1685, 2014, ISSN: 1523-1747 (Electronic)
0022-202X (Linking). @article{RN866,
title = {TGF-beta-induced (TGFBI) protein in melanoma: a signature of high metastatic potential},
author = {Lauden, L. and Siewiera, J. and Boukouaci, W. and Ramgolam, K. and Mourah, S. and Lebbe, C. and Charron, D. and Aoudjit, F. and Jabrane-Ferrat, N. and Al-Daccak, R.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24499734},
doi = {10.1038/jid.2014.20},
issn = {1523-1747 (Electronic)
0022-202X (Linking)},
year = {2014},
date = {2014-01-01},
journal = {J Invest Dermatol},
volume = {134},
number = {6},
pages = {1675-1685},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Boukouaci, W.; Lauden, L.; Siewiera, J.; Dam, N.; Hocine, H. R.; Khaznadar, Z.; Tamouza, R.; Borlado, L. R.; Charron, D.; Jabrane-Ferrat, N.; Al-Daccak, R. Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence Journal Article In: Cardiovasc Res, vol. 104, no. 2, pp. 290-302, 2014, ISSN: 1755-3245 (Electronic)
0008-6363 (Linking). @article{RN865,
title = {Natural killer cell crosstalk with allogeneic human cardiac-derived stem/progenitor cells controls persistence},
author = {Boukouaci, W. and Lauden, L. and Siewiera, J. and Dam, N. and Hocine, H. R. and Khaznadar, Z. and Tamouza, R. and Borlado, L. R. and Charron, D. and Jabrane-Ferrat, N. and Al-Daccak, R.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25213554},
doi = {10.1093/cvr/cvu208},
issn = {1755-3245 (Electronic)
0008-6363 (Linking)},
year = {2014},
date = {2014-01-01},
journal = {Cardiovasc Res},
volume = {104},
number = {2},
pages = {290-302},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
Bahraoui, E.; Briant, L.; Chazal, N. E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein Journal Article In: Virol J, vol. 11, pp. 214, 2014, ISSN: 1743-422X (Electronic)
1743-422X (Linking). @article{RN876,
title = {E5564 inhibits immunosuppressive cytokine IL-10 induction promoted by HIV-1 Tat protein},
author = {Bahraoui, E. and Briant, L. and Chazal, N.},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25471526},
doi = {10.1186/s12985-014-0214-z},
issn = {1743-422X (Electronic)
1743-422X (Linking)},
year = {2014},
date = {2014-01-01},
journal = {Virol J},
volume = {11},
pages = {214},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
|
