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

Renaud Snanoudj Nassim Kamar 1 Elisabeth Cassuto 2 Sophie Caillard 3 Marie Metzger 4 Pierre Merville 5 Antoine Thierry 6 Isabelle Jollet 7 Philippe Grimbert 8 Dany Anglicheau 9, 10 Marc Hazzan 11 Gabriel Choukroun 12 Bruno Hurault de Ligny 13 Bénédicte Janbon 14 Vincent Vuiblet 15 Anne Devys 16 Yann Le Meur 17, 18 Michel Delahousse 19 Emmanuel Morelon 20 Elodie Bailly 21 Sophie Girerd 22 Kahina Amokrane 23 Christophe Legendre 9, 10 Alexandre Hertig 24 Eric Rondeau 24 Jean-Luc Taupin 23
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 Service de Néphrologie [Amiens]
13 Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen]
14 Transplantation rénale [CHU Grenoble]
15 Hôpital Maison Blanche
16 Etablissement français du sang [Angers]
17 LBAI - Lymphocyte B et Auto-immunité
18 CHU - BREST - Nephrologie - CHRU Brest - Service de Nephrologie
19 Hôpital Foch [Suresnes]
20 Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France - Service de néphrologie, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, France
21 Service de Néphrologie et d’Immunologie Clinique [CHRU Tours]
22 Service de Néphrologie [CHRU Nancy]
23 Service d'Immunologie et d'Histocompatibilité
24 Service de néphrologie et de transplantation rénale [CHU Tenon]
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.
Keywords : kidney transplantation HLA mismatching acute rejection antibody-mediated rejection epitopes immunosuppression minimization
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Journal articles
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https://hal.univ-brest.fr/hal-02190537
Contributor : Geneviève Michel <>
Submitted on : Monday, July 22, 2019 - 3:20:46 PM
Last modification on : Wednesday, October 14, 2020 - 4:07:04 AM

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UNIV-BREST | HCL | CESP | UVSQ | COMUE-NORMANDIE | IMMUNO | IBSAM | UNIV-PARIS7 | UNICAEN | USPC | UNIV-PARIS

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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, Nature Publishing Group, 2019, 95 (6), pp.1471-1485. ⟨10.1016/j.kint.2018.12.029⟩. ⟨hal-02190537⟩

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