Dominique Charron

Pierre and Marie Curie University - Paris 6, Lutetia Parisorum, Île-de-France, France

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Publications (170)839.78 Total impact

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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; · 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; · 5.94 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; · 2.81 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. · 0.30 Impact Factor
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    ABSTRACT: 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.
    Transplantation 05/2014; · 3.78 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. · 3.53 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; · 6.19 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 01/2014; 8(4):430-40. · 1.00 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 01/2014; · 2.81 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. 01/2014; 165:135–141.
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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; · 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. · 51.66 Impact Factor
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    ABSTRACT: A soluble isoform of MHC class I chain-related molecule A (soluble MICA), generated by proteolytic shedding from the membrane-bound MICA of various tumor cells, has been shown to downregulate both the expression of natural killer group 2-member D receptor and the cytotoxic function of effectors cells and was postulated as a mechanism for tumor immune evasion. Its effect on the expression of cytokines by the effector cells remained unexplored. Here we demonstrate that the sMICA molecules upregulate interferon gamma expression by interleukin-12/interleukin-18-activated CD3(-)CD56(+) natural killer cells, witnessing the pro-inflammatory effect of soluble MICA. Overall, these data are in line with our previous observations that the raised serum levels of soluble MICA, following allogeneic hematopoietic stem cell transplantation, confer susceptibility to and the presence of pre-transplantation anti-MICA antibodies in the patient's serum confer protection against chronic graft versus host disease.
    Human immunology 08/2013; · 2.55 Impact Factor
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    ABSTRACT: Humoral immune responses during heart transplantation may result in antibody-mediated rejection (AMR), which is now taken into account on endomyocardial biopsy (EMB) specimens and ranked according to the pathologic AMR (pAMR) grades of the International Society for Heart and Lung Transplantation classification. This classification might benefit from new immunohistological markers and validation by others biomarkers, namely donor-specific antibodies (DSA). From the 293 protocol EMBs performed in 113 patients in our institution during a 1-year period for this prospective study, 280 EMB specimens were available with both histology and immunohistochemistry. C4d and labeling of intravascular cells by cluster of differentiation (CD) 68 were performed on paraffin sections. Available sera (n = 150) concomitant of EMB specimens were tested for the presence of DSA. All of the pAMR+ EMB specimens, along with a set of randomized pAMR0 EMB specimens, were immunolabeled for mammalian target of rapamycin (mTOR) effectors, phosphorylated 70 S6-kinase (p70S6K) and phosphorylated S6 ribosomal protein (pS6RP). AMR was diagnosed in 37 EMB specimens (13.2%): 1 pAMR1(I+), 27 pAMR1(H+), and 9 pAMR2. The proportion of DSA-positive EMB varied according to the pAMR grade, with pAMR0, pAMR1(H+), and pAMR2 EMB presenting 17.6%, 77.3%, and 100% of DSA-positivity, respectively. Among the 30 pAMR+ specimens with available DSA testing and the 30 pAMR0 randomized specimens, mTOR pathway immunohistochemistry showed endothelial cell positivity for p70S6K in 17 pAMR+ EMB specimens (56.7%) and in 1 pAMR0 EMB specimen (3.3%). pS6RP was detected in 8 pAMR+ EMB specimens (26.7%) and in 1 pAMR0 EMB specimen (3.3%). p70S6K and pS6RP immunohistochemistry afford new markers of AMR on EMB specimens because their expression is correlated with microcirculation inflammation and DSA. The correlation of DSA with pAMR grade suggests that this grading system is valid.
    The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 08/2013; 32(8):769-76. · 3.54 Impact Factor
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    ABSTRACT: BACKGROUND: New methods of solid-phase assays, such as Luminex assay, with high sensitivity in detecting anti-human leukocyte antigen (HLA) antibodies (Abs), have increased the proportion of sensitized candidates waiting for lung transplantation (LTx). However, how to apply these results clinically during graft allocation is debated: strict exclusion of candidates with Luminex-positive results can lead to lost opportunities for Tx. We retrospectively analyzed the clinical impact of pre-LTx Luminex-detected Abs on post-LTx outcomes for patients who underwent LTx before the availability of Luminex assay. METHODS: We analyzed data for 56 successive patients who underwent LTx before 2008 and were considered to not have anti-HLA Abs by then-available methods of detection at the date of their LTx. Pre-LTx sera from these patients were retested by Luminex assay. Using log-rank test, freedom from bronchiolitis obliterans syndrome (BOS) and graft survival were compared between patients with and without pre-LTx Luminex-detected anti-HLA Abs classes I and II and donor-specific Abs (DSA) classes I and II. RESULTS: Freedom from bronchiolitis obliterans syndrome was lower, and mortality was higher for patients with than those without pre-LTx Luminex-detected DSA class II (P=0.004 and P=0.007, respectively) but did not differ for patients with and without DSA class I or anti-HLA Abs class I or II. CONCLUSIONS: It suggests to avoid attributing graft with forbidden antigens to sensitized candidates with Luminex-detected DSA class II and to evaluate the role of specific posttransplantation protocols for LTx candidates who require emergency LTx.
    Transplantation 01/2013; · 3.78 Impact Factor
  • Dominique Charron, Reem Al-Daccak
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    ABSTRACT: Stem cell based strategies are fast track, novel, alternative therapies to repair damaged tissues of chronic diseases and have raised great hopes for incurable heart failure in particular. Various stem/progenitor populations are being put forward as potential therapies to achieve cardiac repair/regeneration. The recently described cardiac-derived progenitor/stem cells (CPC) received intensive investigation given their inherent programming to reconstitute the damaged myocardium. Clinical application of autologous cells provided convincing evidence of feasibility and efficiency but limited availability, and pointed out that the use of allogenic cells via cell banks, if proven safe, are a more realistic proposition for cardiac repair. Our recent findings reinforced this notion by demonstrating that the inherent immune features of human CPC shift their behavior within the allogenic settings towards the delivery of signals that promote the development, maintenance, and functioning of a PD-L1/PD1 mediated immune-modulator antiinflammatory reparative response, rather than a detrimental conventional allogenic process. In this context, we discuss how this allogenic immune response, if balanced, can be part of the dynamic and durable mechanisms proposed as critical to sustain cardiac regeneration and repair and propose, based on knowledge of transplantation practice strategies, to reach such balance.
    Clinical transplants 01/2013;
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    ABSTRACT: Rejection is still the major cause of allograft loss following organ transplantation and a more complete comprehension of the alloimmune response is required in order to develop new therapeutic approaches. Allogenicity is primarily generated by the expression of major histocompatibility complex (MHC) molecules in the donor organ. Graft microvascular endothelial cells express both HLA class I and class II molecules. They are the first target of the allogeneic response because of their vascular localization and are also able to present antigen to recipient T cells. The endothelium can therefore be considered as both a stimulator of and a target for alloimmune responses and both aspects require further study. We have established a model of constitutive expression of HLA-DR by human microvascular endothelial cells following transduction with a lentiviral vector. This model was employed in a study demonstrating that endothelial cells can induce allogeneic expansion of regulatory and pro-inflammatory CD4(+) T lymphocyte subsets. Because microvascular endothelial cells rapidly lose their expression of HLA-DR ex vivo, this experimental system of lentiviral-mediated expression of HLA-DR allows the study of alloantigen presentation without requiring addition of inflammatory cytokines and thus provides a model for the study of the intra-graft allogeneic CD4(+) T cell response at the single-cell level.
    Methods in molecular biology (Clifton, N.J.) 01/2013; 960:461-472. · 1.29 Impact Factor
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    ABSTRACT: The rapamycin-inducible gene regulation system was designed to minimize immune reactions in man and may thus be suited for gene therapy. We assessed whether this system indeed induces no immune responses. The protein components of the regulation system were produced in the human cell lines HEK 293T, D407, and HER 911 following lentiviral transfer of the corresponding genes. Stable cell lines were established, and the peptides presented by major histocompatibility complex class I (MHC I) molecules on transduced and wild-type (wt) cells were compared by differential mass spectrometry. In all cell lines examined, expression of the transgenes resulted in prominent changes in the repertoire of MHC I-presented self-peptides. No MHC I ligands originating from the transgenic proteins were detected. In vitro analysis of immunogenicity revealed that transduced D407 cells displayed slightly higher capacity than wt controls to promote proliferation of cytotoxic T cells. These results indicate that therapeutic manipulations within the genome of target cells may affect pathways involved in the processing of peptide antigens and their presentation by MHC I. This makes the genomic modifications visible to the immune system which may recognize these events and respond. Ultimately, the findings call attention to a possible immune risk.Molecular Therapy - Nucleic Acids (2013) 2, e75; doi:10.1038/mtna.2013.3; published online 12 February 2013.
    Molecular therapy. Nucleic acids. 01/2013; 2:e75.
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    ABSTRACT: BACKGROUND: Prenatal exposure to viruses or parasites with tropism for the central nervous system is one of the risk factors for psychotic disorders. However, the relationship between past exposure to Toxoplasma gondii (T. gondii) and incidence of bipolar disorders (BD) is poorly documented across populations. METHODS: We explored the potential association between T. gondii exposure and BD in France, a country of high prevalence of Toxoplasmosis, comparing the prevalence of serological markers (IgG/IgM class antibodies) for T. gondii infection in 110 BD patients and 106 healthy controls all living in France. In a subgroup of 42 patients and 42 controls we also evaluated the levels of interleukin 6 (IL-6) transcripts, an adjunct marker of inflammation. RESULTS: We found that the sero-positive group for IgG antibodies to T. gondii had a 2.7 fold odds of having BD as compared to the sero-negative group (OR=2.17 CI 95%=1.09-4.36, p=0.028). Despite the fact that BD patients had significantly higher levels of IL-6 than the non-patient controls, no notable association between T. gondii status and IL-6 transcript levels was found. We did not find any clinical or demographic correlates of Toxoplasma exposure in the study population. LIMITATIONS: Our results are to be interpreted with caution because of our small sample size. RESULTS: We confirm the association between seropositive status to T. gondii and bipolar disorders reported in other populations and extend it to French patients. Our data strengthen the importance of early detection of T. gondii infected patients in order to propose specific and adequate treatments.
    Journal of affective disorders 12/2012; · 3.76 Impact Factor
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    ABSTRACT: Background. Graft failure is a major complication after unrelated cord blood transplantation. Presence of HLA-antibodies before cord blood transplantation may impact graft failure. Design and Methods. To analyze the effect of anti-HLA-antibodies on unrelated cord blood transplantation outcomes, we analyzed 294 unrelated cord blood transplant recipients after reduced intensity conditioning regimen. The majority of the patients (82%) were transplanted for malignancies, 60% with double-unrelated cord blood transplant, 63% were HLA mismatched. Retrospectively, pre-unrelated cord blood transplant serum was tested for HLA-Ab using LuminexTM platform. Results were interpreted as mean fluorescence intensity (MFI) against donor-specific mismatch. Results. Among 62 recipients (23%) who had anti-HLA- antibodies before unrelated cord blood transplant, 14 patients had donor specific anti-HLA-antibodies (DSA) (7 were donor-specific- anti-HLA-antibodies for single-unrelated cord blood transplant and 7 for double- unrelated cord blood transplant). Donor-specific- anti-HLA-antibodies threshold ranged from 1620-17629 of mean fluorescence intensity (MFI). Cumulative incidence of day-60 neutrophil engraftment was 76%. It was 44% for recipients with donor-specific- anti-HLA-antibodies and 81% in those without donor-specific- anti-HLA-antibodies (p=0.006). The cumulative incidence of 1-year transplant related mortality was 46% in patients with donor-specific- anti-HLA-antibodies and 32% in those without antibodies (p=0.06). The presence of donor-specific-anti-HLA-antibodies was associated with a trend for decreased survival rate (42% vs. 29%, p=0.07). Conclusions. Donor-specific-anti-HLA-antibody in recipients of unrelated cord blood transplant is associated with graft failure and decreased survival. Patient's screening for donor-specific-anti-HLA-antibodies before unrelated cord blood transplantation is recommended before choosing a HLA mismatched cord blood unit. Whenever possible it is important to avoid selecting a unit when the patient has donor-specific-anti-HLA-antibodies against.
    Haematologica 12/2012; · 5.94 Impact Factor

Publication Stats

3k Citations
839.78 Total Impact Points

Institutions

  • 2014
    • Pierre and Marie Curie University - Paris 6
      Lutetia Parisorum, Île-de-France, France
  • 1998–2014
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2008–2013
    • Paris Diderot University
      • Institut Universitaire d'Hématologie (IUH)
      Lutetia Parisorum, Île-de-France, France
    • Université Paris-Sud 11
      Orsay, Île-de-France, France
  • 2012
    • Institut National d'Hygiène du Maroc
      Rabat, Rabat-Salé-Zemmour-Zaër, Morocco
  • 2002–2012
    • Institut Universitaire de France
      Lutetia Parisorum, Île-de-France, France
  • 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
  • 1999–2011
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
  • 2009
    • Institut Jacques Monod
      Lutetia Parisorum, Île-de-France, France
  • 2004–2007
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
    • Centre Hospitalier Universitaire de Québec (CHUQ)
      Québec, Quebec, Canada
  • 2006
    • Centre Hospitalier de Versailles
      Versailles, Île-de-France, France
  • 2005
    • The Newcastle upon Tyne Hospitals NHS Foundation Trust
      Newcastle-on-Tyne, England, United Kingdom
  • 1992–1994
    • Institut des Systèmes Complexes, Paris Île-de-France
      Lutetia Parisorum, Île-de-France, France