Dominique Charron

Université Paris-Est Créteil Val de Marne - Université Paris 12, Créteil, Île-de-France, France

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Publications (265)1441.93 Total impact

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    ABSTRACT: The association between Toxoplasma gondii seropositivity and respectively Bipolar Disorder (BD) and Schizophrenia/Schizoaffective disorder (SZ) is one of the most studied link between one pathogen and psychiatric disorders. The aim of the present study was thus to retrospectively determine if the administration of an antipsychotic and/or a mood stabilizer having known in vitro Anti-Toxoplasmic Activity (TATA+) was associated with a better clinical outcome in a population of 152 BD or 114 SZ patients and seropositive for T. gondii infection compared to patients receiving a treatment without anti-toxoplasmic activity (TATA-).
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    ABSTRACT: Background Extensively burned patients receive iterative blood transfusions and skin allografts that often lead to HLA sensitization, and potentially impede access to vascularized composite allotransplantation (VCA).Methods In this retrospective, single center study, anti-HLA sensitization was measured by single-antigen-flow-bead analysis in patients with deep, second and third degree burns over ≥40% total body surface area (TBSA). Association of HLA-sensitization with blood transfusions, skin allografts, and pregnancies was analyzed by bivariate analysis. The eligibility for transplantation was assessed using calculated panel reactive antibodies (cPRA).ResultsTwenty-nine patients aged 32±14 years, including 11 women, presented with a mean burned TBSA of 54±11%. Fifteen patients received skin allografts, comprising those who received cryopreserved (n=3) or glycerol preserved (n=7) allografts, or both (n=5). An average 36±13 packed red blood cell (PRBC) units were transfused per patient. In sera samples collected 38±13 months after the burns, all patients except one presented with anti-HLA antibodies, of which 13 patients (45%) had complement-fixing antibodies. Eighteen patients (62%) were considered highly sensitized (cPRA≥85%). Cryopreserved, but not glycerol preserved skin allografts, history of pregnancy, and number of PRBC units were associated with HLA-sensitization.Conclusions Extensively burned patients may become highly HLA sensitized during acute care, and hence not qualify for VCA. Alternatives to skin allografts might help preserve their later access to VCA.This article is protected by copyright. All rights reserved.
    Transplant International 02/2015; DOI:10.1111/tri.12540 · 3.16 Impact Factor
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    ABSTRACT: Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.
    PLoS ONE 01/2015; 10(3):e0119702. DOI:10.1371/journal.pone.0119702 · 3.53 Impact Factor
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    ABSTRACT: Objectives Non-classical HLA-E molecules may influence the disease susceptibility and phenotype including treatment response in chronic inflammatory disorders such as Rheumatoid Arthritis (RA) by virtue of their capacity to modulate innate immune processes. This study was carried out to investigate the role of HLA-E polymorphism in RA susceptibility, clinical and serological phenotype as well as treatment response. Methods Genomic DNA from 221 RA patients and 200 healthy controls (HC) were typed for HLA-E rs2844724 (C/T) and rs1264457 (HLA-E*01:01/*01:03) single nucleotide polymorphisms (SNPs) using the TaqMan 5'nuclease assay consisting of allele-specific fluorogenic oligonucleotide probes. Results Our study did not find any association between HLA-E polymorphism and RA susceptibility or disease phenotype. However, it was observed that the frequency of HLA-E*01:03 allele was higher in all RA cases (Pc = 0.03,OR = 3.02, 95% CI = 1.06–9.39), young onset RA (YORA) (Pc = 0.03, OR = 3.20, 95% CI = 1.11–9.98) and female RA (Pc = 0.04, OR = 3.04, 95% CI = 1.06–9.46) patients who responded well (good responders) to a combination of non-biological disease modifying anti rheumatic drugs (DMARDs), methotrexate (MTX) and hydroxychloroquine (HCQ) as compared to non-responders. Moreover, the frequency of rs2844724 T allele and TT genotype was observed to be higher in patients with low titers of rheumatoid factor (RF) than those with high titers (90% vs. 77% and 79% vs. 59% respectively), although the difference did not reach statistical significance. Conclusion The results of our study suggest that HLA-E rs1264457 may influence the patient response to treatment with methotrexate-based DMARD therapy. Thus, it may be a useful genetic marker for treatment response in patients with RA.
    Indian Journal of Rheumatology 12/2014; DOI:10.1016/j.injr.2014.08.002
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    ABSTRACT: Effective immunosuppression is mandatory to prevent graft-vs-host disease and to achieve successful clinical outcome of hematopoietic stem cell transplantation. Here, we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporin metabolism and activity influence the incidence of graft-vs-host disease in patients who underwent stem cell transplantation for hematological disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T-cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-vs-host disease prevalence. Indeed, an increased risk of acute graft-vs-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (HR=3.04; p=0.002), nuclear factor of activated T-cells (cytoplasmic 1) (HR=2.69; p=0.004), adenosine triphosphate-binding cassette sub-family C2 (HR=3.53; p=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (HR=3.67; p=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-vs-host disease (HR=0.32-0.41; p=0.0009-0.008) those of nuclear factor of activated T-cells (cytoplasmic 2) are found to increase such risk (HR=3.85; p=0.0004). None of the tested single nucleotide polymorphisms was associated with chronic graft-vs-host disease occurrence. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of germline biomarkers in predicting acute graft-vs-host disease. Further investigations are warranted to improve our understanding of these relationships to personalize immunosuppressive therapy and optimize outcomes. Copyright © 2014, Ferrata Storti Foundation.
    Haematologica 11/2014; DOI:10.3324/haematol.2014.109884 · 5.94 Impact Factor
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    ABSTRACT: Background: Local inflammation is a potential cause of humoral alloimmune responses in renal transplantation, and de novo donor-specific anti-human leucocyte antigen antibodies (dnDSAs) have been associated with a history of acute rejection. Methods: We investigated the frequencies and consequences of dnDSAs after a first episode of acute T-cell-mediated rejection (index TCMR) in previously unsensitized kidney transplant recipients. Results: Of the 1,054 patients who underwent kidney transplantation between September 2004 and December 2010 at our center, we identified 75 unsensitized patients with at least one TCMR. Index TCMRs were diagnosed 4.4+/-6.8 months after transplantation. The dnDSAs were assessed using the highly sensitive single-antigen human leukocyte antigen bead assay 5.1+/-3.9 months after the index TCMR and were detected in 16 patients (21%). Patients who developed dnDSAs were more likely to have experienced pre-transplant sensitizing events and were indistinguishable in their clinical, biologic, and histologic variables at the time of index TCMR, although the tubulitis scores tended to be higher (P=0.079). These patients experienced a significantly higher incidence of subsequent antibody-mediated rejection episodes (P<0.001), but reduced death-censored graft survival was not observed after a median follow-up of 5.5 years post-transplantation. Follow-up biopsies revealed increased antibody-mediated changes with significantly higher glomerulitis scores and numerically higher C4d staining scores. Conclusion: Monitoring anti-human leukocyte antigen antibodies after cellular rejection may be useful, especially among patients with a history of pretransplant exposure to alloantigens, to predict subsequent humoral events and their consequences.
    Transplantation 10/2014; DOI:10.1097/TP.0000000000000448 · 3.78 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving both genetic and environmental factors. Polymorphisms of genes encoding nitric oxide synthase (NOS) and antioxidant glutathione-S transferases (GSTs) have been associated with various tumors. We examined the combined role of NOS3, NOS2 and GST polymorphisms in NPC risk in Tunisians. We found that NOS3-786C allele and -786 CC genotype, NOS3+894T allele and +894 GT+TT genotypes, NOS2-277 G allele and -277 GG genotype, and GSTT1 del/del genotype, are more prevalent in NPC patients as compared to healthy controls. Our results suggest that genetically driven dysfunction in red-ox stress pathway could augment the risk in NPC-susceptible individuals. Copyright © 2014 Elsevier GmbH. All rights reserved.
    Immunobiology 10/2014; 220(1):20-25. DOI:10.1016/j.imbio.2014.09.021 · 2.81 Impact Factor
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    ABSTRACT: Bipolar disorders (BD) are chronic, multisystem and multifactorial disorders with significant lifetime morbidity, mortality and socio-economic burden. Understanding the underlying genetic and disease triggering environmental factors should improve diagnosis, prognosis, prevention and therapeutic management of the disease. Since intestinal innate dysimmunity seems to play a significant role in the etiopathogeny of BD, we explored in a sample of French Caucasian BD patients, the genetic polymorphisms of NOD2 (nucleotide-binding oligomerization domain containing 2) gene, a key player in such immunity. We found a Caucasian–specific ‘standing’ variation to be associated with BD. The significance of this finding is discussed in the context of Crohn's disease as well as the complex function of NOD2 in innate immunity.
    Immunobiology 10/2014; 219(10). DOI:10.1016/j.imbio.2014.06.003 · 2.81 Impact Factor
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    ABSTRACT: Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are promising candidates for cardiac repair. They interact with T cells, major effectors of the adaptive immune response, inducing ÒparacrineÓ anti-inflammatory effects that could sustain tissue repair/regeneration. Natural killer (NK) cells are major effectors of the innate immune system that might influence the persistence of therapeutic stem/progenitor cells. Therefore, to get through successful clinical translation and anticipate allogeneic hCPC persistence, we defined their crosstalk with NK cells under steady state and inflammatory conditions.
    Cardiovascular Research 09/2014; 104(2). DOI:10.1093/cvr/cvu208 · 5.81 Impact Factor
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    ABSTRACT: ProblemTo investigate the possible association of Natural Killer Group (NKG) receptors gene polymorphisms and MHC class I chain-related protein A (MICA) gene polymorphism with recurrent miscarriage (RM).Methods Seven SNPs in NKG2D gene (rs1049174, rs2255336, rs2617160, rs2617161, rs2246809, rs2617169, and rs2617170), one SNP in NKG2A gene (rs1983526), and one SNP in MICA gene (MICA129) were assessed by allelic discrimination (real-time PCR) in both patients and control women.ResultsThe rs2617170 T/T genotype significantly protected against RM [OR (95%) = 0.63 (0.40–0.98)]. The NKG2D haplotypes analysis on the basis of pairwise LD revealed two haplotype blocks. In block1, we found an increased frequency of CAT (Pc = 0.007; OR = 2.13; 95% CI = 1.24–3.68) and GGA haplotypes (Pc = 0.041; OR = 2.02; 95%CI = 1.03–3.96) and reduced frequency of CAA haplotype (Pc = 0.027; OR = 0.72; 95% CI = 0.54–0.96) in patients. In block2, increased frequency of GATG haplotype (Pc = 10−4; OR = 9.25; 95% CI = 3.04–28.12) and reduced frequency of ATTC haplotype (Pc = 0.035; OR = 0.69; 95%CI = 0.50–0.97) were seen in patients.Conclusion The NKG2D gene polymorphisms may influence the success of pregnancy in Tunisian women.
    American Journal Of Reproductive Immunology 09/2014; 72(6). DOI:10.1111/aji.12314 · 3.32 Impact Factor
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    ABSTRACT: Natural killer cells are the first lymphocyte subset to reconstitute, and play a major role in early immunity after allogeneic hematopoietic stem cell transplantation. Cells expressing the activating receptor NKG2C seem crucial in the resolution of cytomegalovirus episodes, even in the absence of T-cells. We prospectively investigated Natural Killer cells reconstitution in a cohort of 439 adult recipients who underwent non T-cell depleted allogeneic hematopoietic stem cell transplantation between 2005 and 2012. Freshly collected blood samples were analyzed 3, 6, 12 and 24 months after transplantation. Data were studied with respect to conditioning regimen, source of stem cells, underlying disease, occurrence of Graft-versus-Host Disease, and profiles of cytomegalovirus reactivation. In multivariate analysis, we show that the absolute numbers of CD56brightNatural killer cells at month 3 were significantly higher after myeloablative than after reduced intensity conditioning. Acute Graft-versus-Host Disease impaired reconstitution of total and CD56dimNatural killer cells at month 3. In contrast, high Natural killer cell count at month 3 was associated with a lower incidence of chronic Graft-versus-Host Disease, independently from a previous episode of acute Graft-versus-Host Disease and stem cell source. NKG2C+CD56dim and total Natural killer cell count at M3 was lower in patients reactivating CMV between month 0 and month 3, but expanded greatly afterwards. These cells were also less numerous in patients who experienced subsequent reactivation between month 3 and month 6. Our results advocate a direct role of NKG2C-expressing Natural killer cells in the early control of cytomegalovirus reactivation after allogeneic hematopoietic stem cell transplantation.
    Haematologica 08/2014; 99(12). DOI:10.3324/haematol.2014.108407 · 5.94 Impact Factor
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    ABSTRACT: Background Toll-like receptor 2 (TLR2) molecules play a pivotal role in innate immune responses by their ability to recognize and sense a wide repertoire of infectious and endogenous cellular structural elements. Here we evaluated whether genetic variants in TLR2 influence the age of the disease onset in bipolar disorder (BD). Methods DNAs from 571 BD patients 229 early-onset (EO-BD) and 342 late-onset (LO-BD) and 199 healthy controls (HC) were analyzed for the following TLR2 polymorphisms: the 5′-UTR −196 to −174 insertion/deletion (ins/del), the intron 1 rs4696480 A/T, and the exon 3 rs3804099 C/T and rs3804100 C/T. PHASE software was used for haplotype reconstruction. Genetic associations were examined using a chi-square test. Results We found that the TLR2 rs3804099 TT was significantly more prevalent in EO-BD than in LO-BD patients (corrected p (pc)=0.024). After excluding family history of psychiatric disorders, we also found that the TLR2 rs4696480 TT genotype was significantly more prevalent in EO-BD as compared to LO-BD and controls (pc=0.002 and 0.002). Homozygous state for the insTTT haplotype, carrying the above mentioned risk genotypes, was significantly more frequent in EO-BD than in LO-BD patients (pc=0.007) and in EO-BD without family history of psychiatric disorders as compared to (i) those with positive history (pc=0.03), (ii) with LO-BD without family history (pc=0.001) and (iii) with HC (pc=0.009). Limitations Confirmation by replication in independent BD cohorts is warranted. Conclusions Our data suggest the potential role of TLR2 genetic variants in the pathogen-mediated susceptibility to BD.
    Journal of Affective Disorders 08/2014; 165:135–141. DOI:10.1016/j.jad.2014.04.059 · 3.71 Impact Factor
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    ABSTRACT: Rheumatoid arthritis (RA), a chronic inflammatory disease affects up to 1% of the general population. Early diagnosis and treatment are limited by the absence of specific and reliable diagnostic/prognostic biomarkers. This study was carried out in 48 Tamil South Indian RA patients and 49 healthy controls (HC) to identify any cytokine signature(s) that could potentially serve as biomarkers. Expression profiles of Th1, Th2, Th17 and Tregs cell type-specifying cytokines and transcription factors were analyzed using real time quantitative PCR (qPCR) assay. To explore if such expression profiles mirror their steady state plasma levels, a bead-based multiplex fluorescent assay was carried out. We found that the expression of transcription factors T-bet (for Th1), GATA-3 (for Th2) and FoxP3 (for Tregs) were significantly lower in patients than in healthy controls (P<0.0001) similar to lowering of IFNγ (P=0.004) and IL-10 (P=0.04). The transcript levels of IL-12p40 and TNF-α were higher among patients as compared to HC (P<0.0001 and P=0.02, respectively). Circulating levels of assessed cytokines were in general higher in RA patients as compared to controls. These alterations in the expression of transcription factors and cytokines highlight the underlying dysregulation of T cell subsets in RA that reflects a predominantly inflammatory phenotype. Despite dissecting these cellular and molecular processes, no specific signature that could be of diagnostic and/or prognostic value was identified. Additional longitudinal follow-up studies, especially on newly diagnosed treatment-naïve patients are warranted to uncover clinically useful biomarkers of RA.
    Immunobiology 06/2014; 219(10). DOI:10.1016/j.imbio.2014.06.004 · 3.18 Impact Factor
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    ABSTRACT: Nasopharyngeal carcinoma (NPC) is a complex multifactorial disorder involving both genetic and environmental factors. Genetic predisposition linked to the immune system has been associated with various tumors. This involves genetic diversity of the genes encoding the molecules of the immune response such as inflammation and anti-tumor surveillance. In this work, we examined the impact of the immunogenetic diversity on the risk of the NPC in different populations studied. These data show that the interindividual variability of the genetic regulation of immune processes increases the risk of NPC in individuals previously predisposed due to other risk factors (genetic / environmental). This synthesis, in addition to the predictive aspects, could provide innovative research for the development of new therapeutic approaches.
    Annales de biologie clinique 06/2014; 72(3):281-291. DOI:10.1684/abc.2014.0958 · 0.42 Impact Factor
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    ABSTRACT: Background. Activating anti-angiotensin type 1 receptor antibodies (AT1R-AA) have been described in patients with systemic scleroderma, an auto-immune disorder with clinical fibrotic features. Chronic graft-versus-host disease (cGvHD) after hematopoietic stem cell transplantation may have clinical fibrotic features, whose pathogenesis may be similar with systemic sclerosis. Objective. To evaluate the presence of AT1R-AA and their association with clinical and biological symptoms in cGvHD patients. Material and Methods. Sera from 87 patients including 45 extensive cGvHD and 42 hematopoietic stem cell transplantation patients without cGvHD were retrospectively analyzed for the presence of AT1R-AA using an enzymatic immunoassay. Results. The frequency of AT1R-AA was significantly increased (odds ratio [OR]-3.4, P=0.04) in the cGvHD group (24.4%) compared with the non-cGvHD group (7.1%). In the cGvHD group the positivity of AT1R-AA was significantly associated with: i/ the presence of antinuclear antibodies (OR=5.9, P=0.04) ii/a more severe global and organ-specific cGvHD scoring (PG0.05), iii/ the presence of active skin or mucosal erosions (OR=19.2, P<0.01). There was no difference between the number and the types of organs involved by the cGvHD between the AT1R-AA-positive versus AT1R-AA-negative subgroups. Conclusion. This preliminary study suggests a potential role and prognostic value of AT1R-AA in cGvHD.
    Transplantation 05/2014; 98(4). DOI:10.1097/TP.0000000000000182 · 3.78 Impact Factor
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    ABSTRACT: Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis (Mtb). TLR2, TLR4, and VDR polymorphisms were previously associated with tuberculosis (TB) and were here investigated as candidates for pulmonary TB (PTB) susceptibility in a Moroccan population group. Genomic DNA from 343 PTB patients and 203 healthy controls were analyzed for 12 single nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using polymerase chain reaction-based restriction fragment length polymorphism and TaqMan SNP genotyping assays. The TLR2 +597 CT genotype was associated with protection against PTB (corrected p [pc] = 0.04; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06 - 2.57). The VDR [f,b,a,T] haplotype was found to confer protection (pc < 0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 [-16934T,+597C,+1349T] haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but statistical significance was not reached. Finally, cross-analysis between polymorphisms of the three studied genes revealed significant interaction between TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036), suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically with TLR2 SNPs. TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.
    The Journal of Infection in Developing Countries 04/2014; 8(4):430-40. DOI:10.3855/jidc.3820 · 1.27 Impact Factor
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    ABSTRACT: BACKGROUND: Infectious events have been reported as major environmental triggers of thrombotic thrombocytopenic purpura (TTP). We detail here the potential association between infections and TTP.
    Transfusion 02/2014; 54(2):389-397. DOI:10.1111/trf.12263 · 3.57 Impact Factor
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    ABSTRACT: Tumor-produced extracellular matrix (ECM) proteins can be key elements in tumor growth and metastasis. Transforming growth factor beta-inducible (TGFBI) protein is a secreted ECM component that can have dual function in cancer, acting as tumor suppressor or promoter. Although TGFBI is expressed in human melanoma cells, the exact role it might have in melanoma metastasis remains elusive. Assessing the expression and secretion of TGFBI, we show that human metastatic melanomas express and secrete significantly higher amounts of TGFBI, compared with nevus lesions and primary melanoma tumors. Intravenous injection of highly metastatic human melanoma cells expressing shRNA that targets TGFBI assigns a critical role for TGFBI in the formation of melanoma distal metastases in nude mice. In vivo assays demonstrate that TGFBI silencing does not interfere with melanoma cells' dissemination to distal sites but rather with their proliferation and outgrowth within new microenvironment. In line, TGFBI silencing increases melanoma cells motility/invasion/extravasation in vitro but interferes with their progression through the cell cycle, drastically reducing their proliferation. Furthermore, we show that TGFBI is a regulator of cyclins and cyclin-dependent kinases in melanoma. Collectively, our data describe a mechanism of melanoma metastatic outgrowth via promotion of growth/survival by the ECM protein TGFBI.Journal of Investigative Dermatology advance online publication, 6 February 2014; doi:10.1038/jid.2014.20.
    Journal of Investigative Dermatology 01/2014; DOI:10.1038/jid.2014.20 · 6.19 Impact Factor
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    ABSTRACT: Bipolar disorder (BD) is considered as a multifactorial disorder involving complex interactions between genetic and environmental factors, where immune dysfunction is thought to play a key etiopathogenic role. In particular, excess of winter births associated with early-life infections raise the possibility of the implication of innate immunity. Given the pivotal role of Toll-like receptor 4 (TLR-4), a major innate immune sensor molecule, we hypothesized that genetic variations of TLR-4 may be associated to BD. Genomic DNAs from 572 BD patients and 202 healthy controls (HC) were analyzed for the distribution of six single nucleotides polymorphisms (SNPs) scattered along the TLR-4 locus (rs1927914, rs10759932, rs4986790, rs4986791, rs11536889 and rs11536891). Associations between BD and these polymorphisms were examined using the Chi-square test. We found that rs1927914 AA and rs11536891 TT genotype are more frequent in BD patients than in controls (corrected p; pc=.02 and .02 respectively) particularly in early-onset BD patients (pc=.004 and .006) born during the summer season (pc=.02 and .002 respectively). We also found that rs4986790 AG and rs4986791 CT genotypes were significantly associated with presence of autoimmune thyroiditis (pc=.002). Our results are to be confirmed by replication in independent BD cohorts. We report for the first time a genetic association between BD and TLR-4 a major player of innate immunity. Possible mechanisms underlying bipolar disorders linking altered TLR-4 expression and increased susceptibility to infections and/or autoimmunity are discussed.
    Journal of Affective Disorders 10/2013; 152. DOI:10.1016/j.jad.2013.09.043 · 3.76 Impact Factor
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    ABSTRACT: Anti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure. We enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed. The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97). Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.
    New England Journal of Medicine 09/2013; 369(13):1215-26. DOI:10.1056/NEJMoa1302506 · 54.42 Impact Factor

Publication Stats

6k Citations
1,441.93 Total Impact Points

Institutions

  • 2015
    • Université Paris-Est Créteil Val de Marne - Université Paris 12
      • Faculty of medicine
      Créteil, Île-de-France, France
  • 2009–2015
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • University of Paris-Est
      La Haye-Descartes, Centre, France
    • Institut Jacques Monod
      Lutetia Parisorum, Île-de-France, France
  • 2014
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 2008–2014
    • Paris Diderot University
      • Institut Universitaire d'Hématologie (IUH)
      Lutetia Parisorum, Île-de-France, France
  • 1999–2014
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 1998–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2012
    • Institut National d'Hygiène du Maroc
      Rabat, Rabat-Salé-Zemmour-Zaër, Morocco
  • 2011
    • Hôpital Saint-Louis (Hôpitaux Universitaires Saint-Louis, Laboisière, Fernand-Widal)
      Lutetia Parisorum, Île-de-France, France
    • European Institute for Systems Biology & Medicine
      Lyons, Rhône-Alpes, France
  • 2007–2008
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
    • University of Florence
      Florens, Tuscany, Italy
  • 2006
    • Centre Hospitalier de Versailles
      Versailles, Île-de-France, France
  • 2005
    • Finnish Red Cross Blood Service
      Helsinki, Uusimaa, Finland
  • 2004
    • Institut Pasteur
      • Department of Immunology
      Lutetia Parisorum, Île-de-France, France
  • 2003
    • University of Maryland, Baltimore
      Baltimore, Maryland, United States
  • 1992–1997
    • Institut des Systèmes Complexes, Paris Île-de-France
      Lutetia Parisorum, Île-de-France, France
  • 1994
    • Hospital Universitario Reina Sofía
      Cordoue, Andalusia, Spain
  • 1986
    • French National Centre for Scientific Research
      Lutetia Parisorum, Île-de-France, France
  • 1982–1983
    • Stanford Medicine
      • Department of Pathology
      Stanford, California, United States