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.
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.
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.
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.,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.