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.

Available on ORBi :

since 23 November 2022

Statistics

Number of views

40 (5 by ULiège)

Number of downloads

27 (2 by ULiège)

More statistics

Scopus citations^®

Scopus citations^®
without self-citations

OpenCitations

OpenAlex citations

Bibliography

Knechtle, S., Marson, L. &; Morris, P. Kidney Transplantation – Principles and Practice (Elsevier, 2019).
Merrill, J. P., Murray, J. E., Harrison, J. H. & Guild, W. R. Successful homotransplantation of the human kidney between identical twins. JAMA 160, 277–282 (1956). DOI: 10.1001/jama.1956.02960390027008
Snell, G. D. Methods for the study of histocompatibility genes. J. Genet. 49, 87–108 (1948). DOI: 10.1007/BF02986826
Snell, G. D. Studies in histocompatibility. Science 213, 172–178 (1981). DOI: 10.1126/science.7017931
Bohmig, G. A., Eskandary, F., Doberer, K. & Halloran, P. F. The therapeutic challenge of late antibody-mediated kidney allograft rejection. Transpl. Int. 32, 775–788 (2019). DOI: 10.1111/tri.13436
Tambur, A. R. et al. Sensitization in Transplantation: Assessment of Risk (STAR) 2017 Working Group meeting report. Am. J. Transplant. 18, 1604–1614 (2018). DOI: 10.1111/ajt.14752
Schinstock, C. A. et al. A 2020 Banff Antibody-mediated Injury Working Group examination of international practices for diagnosing antibody-mediated rejection in kidney transplantation: a cohort study. Transpl. Int. 34, 488–498 (2021). DOI: 10.1111/tri.13813
Jackson, A. M., Wiebe, C. & Hickey, M. J. The role of non-HLA antibodies in solid organ transplantation: a complex deliberation. Curr. Opin. Organ Transplant. 25, 536–542 (2020). DOI: 10.1097/MOT.0000000000000811
Bahram, S., Bresnahan, M., Geraghty, D. E. & Spies, T. A second lineage of mammalian major histocompatibility complex class I genes. Proc. Natl Acad. Sci. USA 91, 6259–6263 (1994). DOI: 10.1073/pnas.91.14.6259
Carapito, R. & Bahram, S. Genetics, genomics, and evolutionary biology of NKG2D ligands. Immunol. Rev. 267, 88–116 (2015). DOI: 10.1111/imr.12328
Zou, Y., Stastny, P., Susal, C., Dohler, B. & Opelz, G. Antibodies against MICA antigens and kidney-transplant rejection. N. Engl. J. Med. 357, 1293–1300 (2007). DOI: 10.1056/NEJMoa067160
Risti, M. & Bicalho, M. D. MICA and NKG2D: is there an impact on kidney transplant outcome? Front. Immunol. 8, 179 (2017). DOI: 10.3389/fimmu.2017.00179
Baranwal, A. K. & Mehra, N. K. Major histocompatibility complex class I chain-related A (MICA) molecules: relevance in solid organ transplantation. Front. Immunol. 8, 182 (2017). DOI: 10.3389/fimmu.2017.00182
Fuerst, D. et al. Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation. Blood 128, 3169–3176 (2016). DOI: 10.1182/blood-2016-05-716357
Carapito, R. et al. Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. Blood 128, 1979–1986 (2016). DOI: 10.1182/blood-2016-05-719070
Susal, C. & Opelz, G. Impact of HLA matching and HLA antibodies in organ transplantation: a collaborative transplant study view. Methods Mol. Biol. 882, 267–277 (2012). DOI: 10.1007/978-1-61779-842-9_15
Doxiadis, I. I., Smits, J. M., Persijn, G. G., Frei, U. & Claas, F. H. It takes six to boogie: allocating cadaver kidneys in Eurotransplant. Transplantation 77, 615–617 (2004). DOI: 10.1097/01.TP.0000103725.72023.D7
Sasaki, N. & Idica, A. The HLA-matching effect in different cohorts of kidney transplant recipients: 10 years later. Clin. Transpl. 261–282 (2010).
Johnson, R. J. et al. A new UK 2006 National Kidney Allocation Scheme for deceased heart-beating donor kidneys. Transplantation 89, 387–394 (2010). DOI: 10.1097/TP.0b013e3181c9029d
Lim, W. H. et al. HLA-DQ mismatches and rejection in kidney transplant recipients. Clin. J. Am. Soc. Nephrol. 11, 875–883 (2016). DOI: 10.2215/CJN.11641115
Khongjaroensakun, N., Kitpoka, P., Wiwattanathum, P., Sakulchairungrueng, B. & Thammanichanond, D. Influence of HLA-DQ matching on allograft outcomes in deceased donor kidney transplantation. Transplant. Proc. 50, 2371–2376 (2018). DOI: 10.1016/j.transproceed.2018.02.187
Leeaphorn, N. et al. HLA-DQ mismatching and kidney transplant outcomes. Clin. J. Am. Soc. Nephrol. 13, 763–771 (2018). DOI: 10.2215/CJN.10860917
Duquesnoy, R. J. HLAMmatchmaker: a molecularly based donor selection algorithm for highly alloimmunized patients. Transplant. Proc. 33, 493–497 (2001). DOI: 10.1016/S0041-1345(00)02108-4
Duquesnoy, R. J. A structurally based approach to determine HLA compatibility at the humoral immune level. Hum. Immunol. 67, 847–862 (2006). DOI: 10.1016/j.humimm.2006.08.001
Duquesnoy, R. J., Mostecki, J., Hariharan, J. & Balazs, I. Structurally based epitope analysis of major histocompatibility complex class I-related chain A (MICA) antibody specificity patterns. Hum. Immunol. 69, 826–832 (2008). DOI: 10.1016/j.humimm.2008.10.003
Senev, A. et al. Eplet mismatch load and de novo occurrence of donor-specific anti-HLA antibodies, rejection, and graft failure after kidney transplantation: an observational cohort study. J. Am. Soc. Nephrol. 31, 2193–2204 (2020). DOI: 10.1681/ASN.2020010019
Fodil, N. et al. Allelic repertoire of the human MHC class I MICA gene. Immunogenetics 44, 351–357 (1996). DOI: 10.1007/BF02602779
Marsh, S. G. et al. Nomenclature for factors of the HLA system, 2010. Tissue Antigens 75, 291–455 (2010). DOI: 10.1111/j.1399-0039.2010.01466.x
Solez, K. et al. Banff 07 classification of renal allograft pathology: updates and future directions. Am. J. Transplant. 8, 753–760 (2008). DOI: 10.1111/j.1600-6143.2008.02159.x
Therneau, T.M. & Grambsch, P. M. Modeling Survival Data: Extending the Cox Model (Springer, 2000).