The HLA-Cw antigens are distinct in having relatively lower expression on the cell surface compared to the other HLA class I loci. Higher HLA Cw antigens expression was correlated with increased likelihood of cytotoxic T lymphocyte responses. We hypothesized that HLA-Cw mismatches (C MM) of high expression would negatively impact kidney transplant outcomes. We also aimed to estimate the frequency of C MM based on the level of expression. The study included 26,172 solitary kidney transplants from 2000-2013 with available HLA-Cw typing data at the Scientific Registry of Transplant Recipients (SRTR). We converted HLA-Cw antigens into the equivalent expression level according to Apps et al, Science 2013. We analyzed the level of expression of C MM as a categorical and continuous variable in association with the incidence of clinically treated acute rejection, patient and overall graft survival adjusted for donor and recipient characteristics. We also stratified analyses by whether patients had 0-mismatched HLA-A, B, DR (0 ABDR MM) transplants. The study included 77% deceased donor transplant recipients, 13% with 0 ABDR MM and 46% with 0 PRA. 15, 44 & 41 % had 0, 1 & 2 C MM respectively. In the 0 ABDR MM group, 64, 31 & 5% had 0, 1 & 2 C MM respectively. The median of C MM expression was 225 (IQR 111-334). There were no significant differences in 1-year rejection, treating Cw expression score as a continuous variable (AOR=1.00, 95% CI 0.92-1.07). In multivariable models, there was no association of C MM with overall graft (1MM: AHR=1.03, 0.96-1.10 or 2MM AHR=0.97, 0.87-1.08) or patient survival (1MM: AHR=1.05, 0.97-1.14 or 2MM AHR=1.03, 0.90-1.17). Moreover, our data shows that relative to 0 C MM – when considering C MM on a continuum – neither expression of 1-150 (n= 3533, AHR=0.97, 0.86-1.10), 151-300 (n=10,004, AHR=1.03, 0.94-1.14), 301-450 (n=8084, AHR=1.01, 0.91-1.11) nor 451-548 (n=603, AHR=1.06, 0.86-1.31) showed an association with overall graft survival in adjusted models. Results were similar in 0 ABDR MM transplants and when stratified by level of sensitization and donor type. HLA-Cw mismatches are fairly common even in 0 ABDR MM. However, there is no evidence that these mismatches impact kidney transplant outcomes even mismatches involving HLA-Cw antigens with high level of expression or in patients with HLA antibodies.

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