The MHC class I MICA gene is a histocompatibility antigen in kidney transplantation
Raphaël Carapito, Ismaïl Aouadi, Martin Verniquet, Meiggie Untrau, Angélique Pichot, Thomas Beaudrey, Xavier Bassand, Sébastien Meyer, Loïc Faucher, Juliane Posson, Aurore Morlon, И. В. Котова, 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, Frédèric 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
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.