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

[en] The identity of histocompatibility loci, besides human leukocyte antigen (HLA), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45–3.11; P < 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94–7.39; P < 0.001; HR, 9.92; 95% CI: 7.43–13.20; P < 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31–199.41; P = 0.002; HR, 82.67; 95% CI: 33.67–202.97; P < 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05–1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02–2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted. © 2022, The Author(s).

Disciplines :

Immunology & infectious disease

Author, co-author :

Carapito, R.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut National de la Santé et de la Recherche Médicale (INSERM) Franco (Strasbourg)–Japanese (Nagano) Nextgen HLA Laboratory, Strasbourg, France, Laboratoire d’Immunologie, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France

Aouadi, I.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut National de la Santé et de la Recherche Médicale (INSERM) Franco (Strasbourg)–Japanese (Nagano) Nextgen HLA Laboratory, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France

Verniquet, M.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut National de la Santé et de la Recherche Médicale (INSERM) Franco (Strasbourg)–Japanese (Nagano) Nextgen HLA Laboratory, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France

Untrau, M.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut National de la Santé et de la Recherche Médicale (INSERM) Franco (Strasbourg)–Japanese (Nagano) Nextgen HLA Laboratory, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France

Pichot, A.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut National de la Santé et de la Recherche Médicale (INSERM) Franco (Strasbourg)–Japanese (Nagano) Nextgen HLA Laboratory, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France

Beaudrey, T.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France, Nephrology-Transplantation Department, University Hospital, Strasbourg, France

Bassand, X.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France, Nephrology-Transplantation Department, University Hospital, Strasbourg, France

Meyer, S.; Laboratoire d’ImmunoRhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Centre de Recherche d’Immunologie et d’Hématologie, Centre de Recherche en Biomédecine de Strasbourg (CRBS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France, Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, Institut National de la Santé et de la Recherche Médicale (INSERM) Franco (Strasbourg)–Japanese (Nagano) Nextgen HLA Laboratory, Strasbourg, France, Institut Thématique Interdisciplinaire (ITI) de Médecine de Précision de Strasbourg, Strasbourg, France

Faucher, L.; Laboratoire d’Excellence (LabEx) TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France, CHU Nantes, Université de Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, Nantes, France

Posson, J.; Paris Translational Research Center for Organ Transplantation, Institut National de la Santé et de la Recherche Médicale (INSERM), UMR_S 970, Paris, France, Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France

More authors (31 more)

Language :

English

Title :

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

Publication date :

2022

Journal title :

Nature Medicine

ISSN :

1078-8956

eISSN :

1546-170X

Publisher :

Nature Research

Volume :

Issue :

Pages :

989 - 998

Peer reviewed :

Peer Reviewed verified by ORBi

Funding text :

The authors thank Y. Foucher (Nantes University, Nantes, France) and P. Ravaud (Paris Descartes University, Paris, France) for discussing the statistical approaches, and E. Nourisson for technical assistance. This work was supported by France’s National Research Agency (Agence Nationale de Recherche; ANR), the Investment for the Future Program (Programme des Investissements d’Avenir; PIA) through a ‘Laboratoire d’Excellence’ (LabEx) TRANSPLANTEX (ANR-11-LABX-0070_TRANSPLANTEX) as well as by Strasbourg’s Interdisciplinary Thematic Institute (ITI) for Precision Medicine, TRANSPLANTEX NG, as part of the ITI 2021–2028 program of the University of Strasbourg, CNRS and INSERM, funded by IdEx Unistra (ANR-10-IDEX-0002) and SFRI-STRAT’US (ANR-20-SFRI-0012), all to S.B. Additional funding was provided by INSERM (UMR_S 1109), the Institut Universitaire de France (IUF), the Fédération Hospitalo-Universitaire (FHU) OMICARE, MSD Avenir ‘Autogen’, all to S.B., and the European regional development fund (European Union) INTERREG V program (project no. 3.2 TRIDIAG and PERSONALIS) to R.C. and S.B.

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