Laboratoire dhistocompatibilite

Strasbourg, France

Laboratoire dhistocompatibilite

Strasbourg, France
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Proust B.,Etablissement Francais du Sang Center Atlantique | Masson D.,Laboratoire dhistocompatibilite | Giraud C.,Etablissement Francais du Sang Center Atlantique | Bouille C.,Etablissement Francais du Sang Center Atlantique | And 3 more authors.
Tissue Antigens | Year: 2015

The novel HLA-B*53:39 allele differs from HLA-B*53:01 by a single nucleotide substitution at codon 45 (ACG>AAG). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sicard A.,Hospices Civils de Lyon | Sicard A.,French Institute of Health and Medical Research | Sicard A.,University of Lyon | Ducreux S.,Laboratoire dHistocompatibilite | And 22 more authors.
Journal of the American Society of Nephrology | Year: 2015

Antibody-mediated rejection (AMR) is a major cause of kidney graft loss, yet assessment of individual risk at diagnosis is impeded by the lack of a reliable prognosis assay. Here, we tested whether the capacity of anti-HLA antibodies to bind complement components allows accurate risk stratification at the time of AMR diagnosis. Among 938 kidney transplant recipients for whom a graft biopsy was performed between 2004 and 2012 at the Lyon University Hospitals, 69 fulfilled the diagnosis criteria for AMR and were enrolled. Sera banked at the time of the biopsy were screened for the presence of donor-specific anti-HLAantibodies (DSAs) and their ability to bind C1q and C3d using flow bead assays. In contrast with C4d graft deposition, the presence of C3d-binding DSA was associated with a higher risk of graft loss (P<0.001). Despite similar trend, the difference did not reach significance with a C1q-binding assay (P=0.06). The prognostic value of a C3d-binding assay was further confirmed in an independent cohort of 39 patients with AMR (P=0.04). Patients with C3d-binding antibodies had worse eGFR and higher DSA mean fluorescence intensity. In a multivariate analysis, only eGFR<30 ml/min per 1.73 m2 (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.46 to 8.70; P=0.005) and the presence of circulating C3d-binding DSA (HR, 2.80; 95% CI, 1.12 to 6.95; P=0.03) were independent predictors for allograft loss at AMR diagnosis. We conclude that assessment of the C3d-binding capacity of DSA at the time of AMR diagnosis allows for identification of patients at risk for allograft loss. © 2015 by the American Society of Nephrology.

PubMed | Service dAnatomopathologie, Hopitaux Universitaires Of Geneva, Laboratoire dHistocompatibilite, Service dHepato Gastroenterologie et Nutrition Pediatriques and Service de Chirurgie Viscerale Pediatrique
Type: | Journal: Pediatric transplantation | Year: 2017

AMR is a risk factor for graft failure after SBTx. We studied impact of DSAs and AMR in 22 children transplanted between 2008 and 2012 (11 isolated SBTx, 10 liver inclusive Tx, and one modified multivisceral Tx). Three patients never developed DSA, but DSAs were found in seven in the pre-Tx period and de novo post-Tx in 19 children. Pathology revealed cellular rejection (15/19), with vascular changes and C4d+. Patients were treated with IV immunoglobulins, plasmapheresis, and steroids. Rescue therapy included antithymocyte globulins, rituximab, eculizumab, and bortezomib. Pathology and graft function normalized in 13 patients, graft loss occurred in two, and death in seven. At the end of the follow-up, 15 children were alive (68%), 13 with functioning graft (59%). Prognosis factors for poor outcome after Tx were the presence of symptoms at AMR suspicion (P +.033). DSAs were often found following SBTx, mostly de novo. Resistant ACR or severe AMR is still difficult to differentiate, with a high need for immunosuppression in both. DSAs may precede development of severe disease and pathology features on the graft: relationship and correlation need to be better investigated with larger groups before and after Tx.

David G.,University of Nantes | Djaoud Z.,University of Nantes | Willem C.,University of Nantes | Legrand N.,University of Nantes | And 8 more authors.
Journal of Immunology | Year: 2013

The interactions of killer Ig-like receptor 2D (KIR2D) with HLA-C ligands contribute to functional NK cell education and regulate NK cell functions. Although simple alloreactive rules have been established for inhibitory KIR2DL, those governing activating KIR2DS function are still undefined, and those governing the formation of the KIR2D repertoire are still debated. In this study, we investigated the specificity of KIR2DL1/2/3 and KIR2DS1/2, dissected each KIR2D function, and assessed the impact of revisited specificities on the KIR2D NK cell repertoire formation from a large cohort of 159 KIR and HLA genotyped individuals. We report that KIR2DL2+ and KIR2DL3 + NK cells reacted similarly against HLA-C+ target cells, irrespective of C1 or C2 allele expression. In contrast, KIR2DL1+ NK cells specifically reacted against C2 alleles, suggesting a larger spectrum of HLA-C recognition by KIR2DL2 and KIR2DL3 than KIR2DL1. KIR2DS2+ KIR2DL2- NK cell clones were C1-reactive irrespective of their HLA-C environment. However, when KIR2DS2 and KIR2DL2 were coexpressed, NK cell inhibition via KIR2DL2 overrode NK cell activation via KIR2DS2. In contrast, KIR2DL1 and KIR2DS2 had an additive enhancing effect on NK cell responses against C1C1 target cells. KIR2DL2/3/S2 NK cells predominated within the KIR repertoire in KIR2DL2/S2+ individuals. In contrast, the KIR2DL1/S1 NK cell compartment is dominant in C2C2 KIR2DL2/S2- individuals. Moreover, our results suggest that together with KIR2DL2, activating KIR2DS1 and KIR2DS2 expression limits KIR2DL1 acquisition on NK cells. Altogether, our results suggest that the NK cell repertoire is remolded by the activating and inhibitory KIR2D and their cognate ligands. Copyright © 2013 by The American Association of Immunologists, Inc.

Sberro-Soussan R.,University of Paris Descartes | Zuber J.,University of Paris Descartes | Suberbielle-Boissel C.,Laboratoire dHistocompatibilite | Candon S.,University of Paris Descartes | And 13 more authors.
American Journal of Transplantation | Year: 2010

Persistence of donor-specific anti-HLA antibodies (DSA) associated with antibody-mediated graft injuries following kidney transplantation predicts evolution toward chronic humoral rejection and reduced graft survival. Targeting plasma cells, the main antibody-producing cells, with the proteasome inhibitor bortezomib may be a promising desensitization strategy. We evaluated the in vivo efficacy of one cycle of bortezomib (1.3 mg/m2 × 4 doses), used as the sole desensitization therapy, in four renal transplant recipients experiencing subacute antibody-mediated rejection with persisting DSA (>2000 [Mean Fluorescence Intensity] MFI). Bortezomib treatment did not significantly decrease DSA MFI within the 150-day posttreatment period in any patient. In addition, antivirus (HBV, VZV and HSV) antibody levels remained stable following treatment suggesting a lack of efficacy on long-lived plasma cells. In conclusion, one cycle of bortezomib alone does not decrease DSA levels in sensitized kidney transplant recipients in the time period studied. These results underscore the need to evaluate this new desensitization agent properly in prospective, randomized and well-controlled studies. © 2010 The American Society of Transplantation and the American Society of Transplant Surgeons.

Aubert O.,Service de Nephrologie Transplantation Adulte | Bories M.-C.,Service de Nephrologie Transplantation Adulte | Suberbielle C.,Laboratoire dHistocompatibilite | Snanoudj R.,Service de Nephrologie Transplantation Adulte | And 7 more authors.
American Journal of Transplantation | Year: 2014

Anti-HLA donor-specific antibodies (DSAs) cause acute and chronic antibody-mediated rejection (AMR). However, the clinical relevance of anti-HLA-C antibodies remains unclear. We evaluated the clinical relevance of the presence of anti-HLA-C DSA at day 0 in renal transplant recipients. In this retrospective, case-controlled study, 608 patients who underwent kidney transplantation between August 2008 and March 2012 were screened for the presence of isolated anti-HLA-C DSA at day 0. A total of 22 renal transplant recipients were selected and followed for a period of 1 year. AMR was classified according to the Banff classification. The 22 patients were compared with 88 immunized patients. Acute AMR was diagnosed in six patients (27.3%). The median level of DSA at day 0 was 1179 (530-17 941). The mean fluorescence intensity in the anti-C group was 4966 (978-17 941) in the AMR group and 981 (530-8012) in the group of patients without AMR. Acute AMR was diagnosed less frequently in the 88 immunized individuals (9.1%) than in the DSA anti-C group (p = 0.033). The level of DSA at day 0 was predictive for AMR (p = 0.017). Patients with a high level of pretransplant anti-HLA-C DSAs are likely to develop acute AMR during the first year after transplantation. In this retrospective, case-controlled study of renal transplant recipients, the authors demonstrate that patients with a high level of pretransplant anti-HLA-C donor-specific antibodies are likely to develop acute antibody-mediated rejection during the first year after transplantation. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Sicard A.,Service de Transplantation Renale Adulte | Sicard A.,University Paris DescartesSorbonne Paris Cite | Amrouche L.,Service de Transplantation Renale Adulte | Amrouche L.,University Paris DescartesSorbonne Paris Cite | And 13 more authors.
American Journal of Transplantation | Year: 2014

The detection of preformed donor-specific alloantibodies (DSA) with multiplex-bead arrays has led to the common observation that individuals without a history of pregnancy, transfusion or transplantation can have circulating anti-HLA antibodies of unknown etiology. We retrospectively analyzed the risk of antibody-mediated rejection (AMR) and graft outcome in 41 kidney transplant recipients with DSA of unknown etiology (DSA cause-unk) at the time of transplantation. Twenty-one patients received a posttransplantation desensitization protocol, and 20 received standard immunosuppressive therapy. The mean number of DSA was 1.4 ± 0.8, ranging from 1 to 5. Complement-dependent cytotoxicity crossmatches were negative for all the patients. Flow cytometry crossmatches were positive in 47.6% of cases. The incidence of acute AMR was 14.6% at 1 year, regardless of the immunosuppressive regimen. No patients experienced graft loss following AMR. At month 12, across the entire population of patients with DSA cause-unk, the outcomes were favorable: the measured glomerular filtration rate was 63.8 ± 16.4 mL/min/1.73 m2, the screening biopsies showed low frequencies of microvascular inflammation and no transplant glomerulopathy, and graft and patient survival were 100%. In conclusion, patients with DSA cause-unk are able to mount AMR but have favorable 1-year outcomes. This study analyzes kidney transplants performed in recipients with preformed donor-specific antibodies but without a history of an HLA-immunizing event, and shows that although these patients may experience antibodymediated rejection, they have a favorable one-year outcome. © 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Burbach M.,AP HP | Suberbielle C.,Laboratoire dHistocompatibilite | Brocheriou I.,AP HP | Brocheriou I.,University Pierre and Marie Curie | And 8 more authors.
Transplantation | Year: 2014

Background: Acute antibody-mediated rejection (AMR) is responsible for up to 20% to 30% of acute rejection after kidney transplantation. New therapeutic agents have recently emerged, such as eculizumab, an anticomplement protein-C5 monoclonal antibody. In the setting of renal transplantation, eculizumab has so far proved effective both for preventive and curative treatments of AMR in sensitized patients and patients diagnosed with severe AMR. Unsuccessful eculizumab treatment has only been reported once in the literature by Stegall et al. (Am J Transplant 2011;11:2405). Methods and Results: We present two cases of AMR resistant to eculizumab after renal transplantation. One patient received the anti-C5 antibody curatively, and the other patient developed AMR while being treated with eculizumab after a relapse of atypical hemolytic uremic syndrome. The peculiarity of these two cases was the absence of C4d deposition in peritubular capillaries as well as the absence of C1q-binding donor-specific anti-human leukocyte antigen alloantibody, as determined retrospectively, suggesting that a complement-independent mechanism underlies the pathogenesis of these AMR. Conclusion: The use of eculizumab in C4d-negative or C1q-negative AMR does not seem effective. Copyright © 2014 by Lippincott Williams & Wilkins.

Loupy A.,French Institute of Health and Medical Research | Loupy A.,University of Paris Descartes | Suberbielle-Boissel C.,Laboratoire dHistocompatibilite | Zuber J.,University of Paris Descartes | And 9 more authors.
Transplantation | Year: 2010

BACKGROUND.: This study assesses the immunologic, functional, and histologic course of kidney recipients with preformed donor-specific alloantibodies (DSA) receiving deceased donor kidneys according to two prophylactic strategies that have been sequentially applied posttransplant. METHODS.: The first strategy combined posttransplant quadritherapy/intravenous immunoglobulin (group 1, n=36) and the second added to the above protocol anti-CD20/plasmapheresis (group 2, n=18). All patients had a concomitant evaluation of glomerular filtration rate, protocol biopsies, and DSA mean intensity of fluorescence (MFI) at 3 month and 1 year posttransplant. RESULTS.: Peak and day-0 class-I or II DSAmax-MFI were similar in both groups. The rate of acute antibody-mediated rejection (AMR) was similar in both groups (19.6% vs. 16.6%, respectively). At 1 year posttransplant, group 2 was characterized by lower microcirculation inflammation lesions (glomerulitis+capilaritis score of 1.8±0.2 vs. 2.7±0.2, respectively, P=0.03), a lower rate of transplant glomerulopathy (7% vs. 38%, P=0.02), and a lower rate of chronic AMR (41.3% vs. 13.3%, respectively, P=0.03). The decline in DSA-MFI from day 0 to 1 year was 44%±13% in group 1 compared with 80%±8% in group 2 (P=0.02). Finally, the 1-year glomerular filtration rate was 43±16 vs. 54±16 mL/min/1.73 m in groups 1 and 2, respectively (P=0.04). CONCLUSION.: This study raises the possibility that a more intensive day 0 prophylactic immunosuppressive strategy combining intravenous immunoglobulin/anti-CD20/plasmapheresis in this high-risk population, despite similar rates of early acute clinical humoral rejection, is associated with significant differences in long-term function and chronic AMR rate. Future prospective randomized studies are needed to assess the best strategies to be applied in light of the pretransplant immunologic risk stratification. Copyright © 2010 by Lippincott Williams & Wilkins.

Hill G.S.,Laboratoire dAnatomie Pathologique | Nochy D.,Laboratoire dAnatomie Pathologique | Nochy D.,University of Paris Descartes | Bruneval P.,Laboratoire dAnatomie Pathologique | And 11 more authors.
Journal of the American Society of Nephrology | Year: 2011

In biopsies of renal allografts, arteriosclerosis is often more severe than expected based on the age of the donor, even without a history of rejection vasculitis. To determine whether preformed donor-specific antibodies (DSAs) may contribute to the severity of arteriosclerosis, we examined protocol biopsies from patients with (n = 40) or without (n = 59) DSA after excluding those with any evidence of vasculitis. Among DSA-positive patients, arteriosclerosis significantly progressed between month 3 and month 12 after transplant (mean Banff cv score 0.65 ± 0.11 to 1.12 ± 0.10, P = 0.014); in contrast, among DSA-negative patients, we did not detect a statistically significant progression during the same time-frame (mean Banff cv score 0.65 ± 0.11 to 0.81 ± 0.10, P = not significant). Available biopsies at later time points supported a rate of progression of arteriosclerosis in DSA-negative patients that was approximately one third that in DSA-positive patients. Accelerated arteriosclerosis was significantly associated with peritubular capillary leukocytic infiltration, glomerulitis, subclinical antibody-mediated rejection, and interstitial inflammation. In conclusion, these data support the hypothesis that donor-specific antibodies dramatically accelerate post-transplant progression of arteriosclerosis. Copyright © 2011 by the American Society of Nephrology.

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