The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation
Carapito, Raphael; Aouadi, Ismail; Verniquet, Martin; Untrau, Meiggie; Pichot, Angélique; Beaudrey, Thomas; Bassand, Xavier; Meyer, Sébastien; Faucher, Loic; Posson, Juliane; Morlon, Aurore; Kotova, Irina; Delbos, Florent; Walencik, Alexandre; Aarnink, Alice; Kennel, Anne; Suberbielle, Caroline; Taupin, Jean-Luc; Matern, Benedict M; Spierings, Eric; Congy-Jolivet, Nicolas; Essaydi, Arnaud; Perrin, Peggy; Blancher, Antoine; Charron, Dominique; Cereb, Nezih; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Garrigue, Valérie; Pernin, Vincent; Weekers, Laurent; Naesens, Maarten; Kamar, Nassim; Legendre, Christophe; Glotz, Denis; Caillard, Sophie; Ladrière, Marc; Giral, Magali; Anglicheau, Dany; Süsal, Caner; Bahram, Seiamak
(2022) Nature Medicine, volume 28, issue 5, pp. 989 - 998
(Article)
Abstract
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
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(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.
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Keywords: General Biochemistry,Genetics and Molecular Biology, Journal Article
ISSN: 1078-8956
Publisher: Nature Publishing Group
Note: Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2022, The Author(s).
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