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Article Dans Une Revue Nature Medicine Année : 2022

The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

1 IRM - Immuno-Rhumatologie Moléculaire
2 Laboratoire International Associé (LIA) INSERM, Strasbourg (France) - Nagano (Japan), Strasbourg, France
3 OMICARE - Fédération Hospitalo-Universitaire
4 FMTS - Fédération de Médecine Translationnelle de Strasbourg
5 GENOMAX [plateforme]
6 UNISTRA - Université de Strasbourg
7 U1064 Inserm - CR2TI - Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology
8 PARCC (UMR_S 970/ U970) - Paris-Centre de Recherche Cardiovasculaire
9 BIOMICA SA [Strasbourg]
10 Etablissement Français du Sang [Nantes]
11 IMoPA - Ingénierie Moléculaire et Physiopathologie Articulaire
12 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
13 HIPI (UMR_S_976 / U976) - Immunologie humaine, physiopathologie & immunothérapie
14 University Medical Center [Utrecht]
15 LIMT - Laboratoire d'Immunogénétique Moléculaire
16 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
17 EFS - alsace strasbourg - Etablissement Français du Sang - Grand Est
18 HistoGenetics – The Genomics Company – NGS & Beyond [Ossining, NY, USA]
19 IRMA - Institut de Recherche Mathématique Avancée
20 U1064 Inserm - CR2TI - Team 4 : Deciphering organ immune regulation in inflammation and transplantation (DORI-t)
21 CHU - Hôpital Lapeyronie [Montpellier]
22 CHU-Liège - Centre Hospitalier Universitaire de Liège
23 KU Leuven - Catholic University of Leuven = Katholieke Universiteit Leuven
24 Infinity - Institut Toulousain des Maladies Infectieuses et Inflammatoires
25 Service Néphrologie et transplantation rénale Adultes [CHU Necker]
26 Service de Cardiologie et Transplantation [CHRU Nancy]
27 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
28 UniversitätsKlinikum Heidelberg
29 Koç University
Benedict M Matern
Eric Spierings
Seiamak Bahram

Résumé

K idney transplantation is the only curative treatment for end-stage renal disease 1. The fact that the first successful kidney transplantation in man was between identical twins 2 , along with seminal work in animal models, hinted strongly that a single genetic locus does not govern the clinical outcome of a transplantation, no matter how relevant (such as the major histocompatibility complex (MHC), human leukocyte antigen (HLA)). Indeed, George Snell, in his landmark 1948 study 3 (as well as subsequent work by himself, and others), identified several dozen histocompatibility loci in the mouse 4 , although close to none has been identified to date in any species (including man). Fast forward to today, and, owing to the development and refinement of country-and continent-wide allocation processes, perioperative handling of the graft and patients, and selective immunosuppressive drugs that improve transplantation survival mainly by alleviating acute T cell-mediated rejection (TCMR), the number of kidney transplantations is continuously increasing worldwide. However, antibody-mediated rejection (ABMR) is recognized as a major cause of late transplantation failure, and its treatment remains challenging 5. In addition to the histological findings, a key feature of ABMR is the presence of donor-specific anti-HLA antibodies (DSA) 6. Nonetheless, in routine clinical care, cases meeting the histological criteria for ABMR but without detectable anti-HLA DSA could represent more than 50% of rejection events 7. These cases might be explained by the presence of pathogenic antibodies that are produced against other, non-HLA, histocompatibility antigens 8. MHC class I chain-related gene A (MICA; GenBank accession: NM_001177519), discovered almost 30 years ago 9 , encodes a polymorphic non-conventional MHC-encoded class I molecule 10. The MICA gene is located, within the HLA complex, 46 kb centromeric to the HLA-B locus 9. Close to 400 MICA alleles have been reported to date 10. The MICA glycoprotein (Uniprot accession: Q96QC4) is expressed on a restricted number of cell types, mainly epithelial and endothelial cells. MICA binds NKG2D, an activating receptor present on the surface of cytotoxic CD8 + αβ and γδ T lymphocytes as well as certain natural killer (NK) cells 10. Fifteen years ago Zou et al. 11 reported the first comprehensive study of the potential involvement of MICA in kidney transplant outcomes. That work, however, was focused only on anti-MICA antibodies and had no information on donor and recipient MICA (mis)matching, a situation that has persisted to date given that no study has analyzed simultaneously the sequence-based molecular MICA matching and the status of both anti-HLA and anti-MICA DSA in a large cohort for which information about all other relevant covariates was available and included in the final analysis (for review see refs. 12,13).
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hal-03762019 , version 1 (26-08-2022)

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Raphael Carapito, Ismail Aouadi, Martin Verniquet, Meiggie Untrau, Angélique Pichot, et al.. The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation. Nature Medicine, 2022, 28 (5), pp.989-998. ⟨10.1038/s41591-022-01725-2⟩. ⟨hal-03762019⟩
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