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

Raphael Carapito; Ismail Aouadi; Martin Verniquet; Meiggie Untrau; Angélique Pichot; Thomas Beaudrey; Xavier Bassand; Sébastien Meyer; Loic Faucher; Juliane Posson; Aurore Morlon; Irina Kotova; Florent Delbos; Alexandre Walencik; Alice Aarnink; Anne Kennel; Caroline Suberbielle; Jean-Luc Taupin; Benedict M Matern; Eric Spierings; Nicolas Congy-Jolivet; Arnaud Essaydi; Peggy Perrin; Antoine Blancher; Dominique Charron; Nezih Cereb; Myriam Maumy-Bertrand; Frédéric Bertrand; Valérie Garrigue; Vincent Pernin; Laurent Weekers; Maarten Naesens; Nassim Kamar; Christophe Legendre; Denis Glotz; Sophie Caillard; Marc Ladrière; Magali Giral; Dany Anglicheau; Caner Süsal; Seiamak Bahram

doi:10.1038/s41591-022-01725-2

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

Raphael Carapito
, Ismail Aouadi
, Martin Verniquet
, Meiggie Untrau
, Angélique Pichot
, Thomas Beaudrey
, Xavier Bassand
, Sébastien Meyer
, Loic Faucher
, Juliane Posson
, Aurore Morlon
, Irina Kotova
, Florent Delbos
, Alexandre Walencik
, Alice Aarnink
, Anne Kennel
, Caroline Suberbielle
, Jean-Luc Taupin
, Benedict M Matern
, Eric Spierings

Nicolas Congy-Jolivet, Arnaud Essaydi, Peggy Perrin, Antoine Blancher, Dominique Charron, Nezih Cereb, Myriam Maumy-Bertrand, Frédéric Bertrand, Valérie Garrigue, Vincent Pernin, Laurent Weekers, Maarten Naesens, Nassim Kamar, Christophe Legendre, Denis Glotz, Sophie Caillard, Marc Ladrière, Magali Giral, Dany Anglicheau, Caner Süsal, Seiamak Bahram

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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 (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.

Original language	English
Pages (from-to)	989-998
Number of pages	10
Journal	Nature Medicine
Volume	28
Issue number	5
Early online date	14 Mar 2022
DOIs	https://doi.org/10.1038/s41591-022-01725-2
Publication status	Published - May 2022

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Carapito, R., Aouadi, I., Verniquet, M., Untrau, M., Pichot, A., Beaudrey, T., Bassand, X., Meyer, S., Faucher, L., Posson, J., Morlon, A., Kotova, I., Delbos, F., Walencik, A., Aarnink, A., Kennel, A., Suberbielle, C., Taupin, J.-L., Matern, B. M., ... Bahram, S. (2022). The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation. Nature Medicine, 28(5), 989-998. https://doi.org/10.1038/s41591-022-01725-2

@article{d8aa2e9b82ac48759ed9a495d0d411f9,

title = "The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation",

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 (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.",

author = "Raphael Carapito and Ismail Aouadi and Martin Verniquet and Meiggie Untrau and Ang{\'e}lique Pichot and Thomas Beaudrey and Xavier Bassand and S{\'e}bastien Meyer and Loic Faucher and Juliane Posson and Aurore Morlon and Irina Kotova and Florent Delbos and Alexandre Walencik and Alice Aarnink and Anne Kennel and Caroline Suberbielle and Jean-Luc Taupin and Matern, \{Benedict M\} and Eric Spierings and Nicolas Congy-Jolivet and Arnaud Essaydi and Peggy Perrin and Antoine Blancher and Dominique Charron and Nezih Cereb and Myriam Maumy-Bertrand and Fr{\'e}d{\'e}ric Bertrand and Val{\'e}rie Garrigue and Vincent Pernin and Laurent Weekers and Maarten Naesens and Nassim Kamar and Christophe Legendre and Denis Glotz and Sophie Caillard and Marc Ladri{\`e}re and Magali Giral and Dany Anglicheau and Caner S{\"u}sal and Seiamak Bahram",

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{\textquoteright}s National Research Agency (Agence Nationale de Recherche; ANR), the Investment for the Future Program (Programme des Investissements d{\textquoteright}Avenir; PIA) through a {\textquoteleft}Laboratoire d{\textquoteright}Excellence{\textquoteright} (LabEx) TRANSPLANTEX (ANR-11-LABX-0070\_TRANSPLANTEX) as well as by Strasbourg{\textquoteright}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{\textquoteright}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 F{\'e}d{\'e}ration Hospitalo-Universitaire (FHU) OMICARE, MSD Avenir {\textquoteleft}Autogen{\textquoteright}, 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{\textquoteright}s National Research Agency (Agence Nationale de Recherche; ANR), the Investment for the Future Program (Programme des Investissements d{\textquoteright}Avenir; PIA) through a {\textquoteleft}Laboratoire d{\textquoteright}Excellence{\textquoteright} (LabEx) TRANSPLANTEX (ANR-11-LABX-0070\_TRANSPLANTEX) as well as by Strasbourg{\textquoteright}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{\textquoteright}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 F{\'e}d{\'e}ration Hospitalo-Universitaire (FHU) OMICARE, MSD Avenir {\textquoteleft}Autogen{\textquoteright}, 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: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = may,

doi = "10.1038/s41591-022-01725-2",

language = "English",

volume = "28",

pages = "989--998",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Research",

number = "5",

}

Carapito, R, Aouadi, I, Verniquet, M, Untrau, M, Pichot, A, Beaudrey, T, Bassand, X, Meyer, S, Faucher, L, Posson, J, Morlon, A, Kotova, I, Delbos, F, Walencik, A, Aarnink, A, Kennel, A, Suberbielle, C, Taupin, J-L, Matern, BM, Spierings, E, Congy-Jolivet, N, Essaydi, A, Perrin, P, Blancher, A, Charron, D, Cereb, N, Maumy-Bertrand, M, Bertrand, F, Garrigue, V, Pernin, V, Weekers, L, Naesens, M, Kamar, N, Legendre, C, Glotz, D, Caillard, S, Ladrière, M, Giral, M, Anglicheau, D, Süsal, C & Bahram, S 2022, 'The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation', Nature Medicine, vol. 28, no. 5, pp. 989-998. https://doi.org/10.1038/s41591-022-01725-2

TY - JOUR

T1 - The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation

AU - Carapito, Raphael

AU - Aouadi, Ismail

AU - Verniquet, Martin

AU - Untrau, Meiggie

AU - Pichot, Angélique

AU - Beaudrey, Thomas

AU - Bassand, Xavier

AU - Meyer, Sébastien

AU - Faucher, Loic

AU - Posson, Juliane

AU - Morlon, Aurore

AU - Kotova, Irina

AU - Delbos, Florent

AU - Walencik, Alexandre

AU - Aarnink, Alice

AU - Kennel, Anne

AU - Suberbielle, Caroline

AU - Taupin, Jean-Luc

AU - Matern, Benedict M

AU - Spierings, Eric

AU - Congy-Jolivet, Nicolas

AU - Essaydi, Arnaud

AU - Perrin, Peggy

AU - Blancher, Antoine

AU - Charron, Dominique

AU - Cereb, Nezih

AU - Maumy-Bertrand, Myriam

AU - Bertrand, Frédéric

AU - Garrigue, Valérie

AU - Pernin, Vincent

AU - Weekers, Laurent

AU - Naesens, Maarten

AU - Kamar, Nassim

AU - Legendre, Christophe

AU - Glotz, Denis

AU - Caillard, Sophie

AU - Ladrière, Marc

AU - Giral, Magali

AU - Anglicheau, Dany

AU - Süsal, Caner

AU - Bahram, Seiamak

N1 - 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).

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/85126238249

U2 - 10.1038/s41591-022-01725-2

DO - 10.1038/s41591-022-01725-2

M3 - Article

C2 - 35288692

SN - 1078-8956

VL - 28

SP - 989

EP - 998

JO - Nature Medicine

JF - Nature Medicine

IS - 5

ER -

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

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