This study investigated the role of MICA in allograft survival in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (HR, 2.12; 95% 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.

This is a retrospective cohort study of 893 kidney transplant recipients between 2004-2013 with available biopsy data and a DNA sample for high-resolution HLA donor/recipient typing to investigate the relationship between HLA molecular mismatches and T-cell mediated rejection (TCMR). 277 patients developed TCMR and 134 developed only borderline changes suggestive of TCMR on at least one biopsy. In multivariable analyses, only the PIRCHE-II scores (Predicted Indirectly ReCognizable HLA Epitopes by recipient HLA class II molecules algorithm) for HLA-DRB1 and HLA-DQB1 were independently associated with the occurrence of TCMR and with allograft failure; this was not the case for HLA class I molecules. If restricted to rejection episodes within the first 3 months after transplantation, only the T-cell epitope targets originating from the donor's HLA-DRB1 and HLA-DQB1, but not class I molecules, were associated with the early acute TCMR. Also, the median number of PIRCHE-II scores for HLA class II was statistically different between the patients with TCMR compared to the patients without TCMR (129, IQR=60-240; vs. 201, IQR=96-298; p<0.0001, respectively). These differences were not observed for class I PIRCHE-II scores.