Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression - Université de Bretagne Occidentale Access content directly
Journal Articles Kidney International Year : 2019

Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression

1 Service de Néphrologie - Immunologie Clinique [Toulouse]
2 CHU Nice - Centre Hospitalier Universitaire de Nice
3 Service de Néphrologie et Transplantation [Strasbourg]
4 CESP - Centre de recherche en épidémiologie et santé des populations
5 Service de Néphrologie-transplantation-dialyse [Bordeaux]
6 Service de Néphrologie-Hémodialyse-Transplantation rénale [CHU Poitiers]
7 EFS - Etablissement français du sang [Poitiers]
8 Service de néphrologie [CHU Henri Mondor]
9 Département de Néphrologie [CHU Necker]
10 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
11 Service de Néphrologie et Transplantation rénale [CHRU-lille]
12 LIRIC - Lille Inflammation Research International Center - U 995
13 MP3CV - Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517
14 Service de Néphrologie-Dialyse-Transplantation [CHU Amiens-Picardie]
15 Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen]
16 Transplantation rénale [CHU Grenoble]
17 Hôpital Maison Blanche
18 Etablissement français du sang [Angers]
19 LBAI - Lymphocytes B, Autoimmunité et Immunothérapies
20 CHU - BREST - Nephrologie - CHRU Brest - Service de Nephrologie
21 Hôpital Foch [Suresnes]
22 Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France - Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France
23 Service de néphrologie et immunologie clinique [CHRU Tours]
24 Service de Néphrologie [CHRU Nancy]
25 Service d'Immunologie et d'Histocompatibilité
26 CHU Tenon [AP-HP]
Renaud Snanoudj
Vincent Vuiblet
Anne Devys
  • Function : Author
  • PersonId : 857129
Alexandre Hertig
  • Function : Author
  • PersonId : 919076
Eric Rondeau
  • Function : Author
  • PersonId : 835505

Abstract

Human leukocyte antigen (HLA) mismatching and minimization of immunosuppression are two major risk factors for the development of de novo donor-specific antibodies, which are associated with reduced kidney graft survival. Antibodies do not recognize whole HLA antigens but rather individual epitopes, which are short sequences of amino acids in accessible positions. However, compatibility is still assessed by the simple count of mismatched HLA antigens. We hypothesized that the number of mismatched epitopes, or ("epitope load") would identify patients at the highest risk of developing donor specific antibodies following minimization of immunosuppression. We determined epitope load in 89 clinical trial participants who converted from cyclosporine to everolimus 3 months after kidney transplantation. Twenty-nine participants (32.6%) developed de novo donor specific antibodies. Compared to the number of HLA mismatches, epitope load was more strongly associated with the development of donor specific antibodies. Participants with an epitope load greater than 27 had a 12-fold relative risk of developing donor-specific antibodies compared to those with an epitope load below that threshold. Using that threshold, epitope load would have missed only one participant who subsequently developed donor specific antibodies, compared to 8 missed cases based on a 6-antigen mismatch. DQ7 was the most frequent antigenic target of donor specific antibodies in our population, and some DQ7 epitopes appeared to be more frequently involved than others. Assessing epitope load before minimizing immunosuppression may be a more efficient tool to identify patients at the highest risk of allosensitization.
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Dates and versions

hal-02190537 , version 1 (25-10-2021)

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Attribution - NonCommercial

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Renaud Snanoudj, Nassim Kamar, Elisabeth Cassuto, Sophie Caillard, Marie Metzger, et al.. Epitope load identifies kidney transplant recipients at risk of allosensitization following minimization of immunosuppression. Kidney International, 2019, 95 (6), pp.1471-1485. ⟨10.1016/j.kint.2018.12.029⟩. ⟨hal-02190537⟩
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