HLA class II-restricted regulatory T cell (Treg) epitopes in IgG (also called “Tregitopes”) have been reported to suppress immune responses to co-administered antigens by stimulating the expansion of natural Tregs (nTregs). Under the current kidney allocation system in the United States, the only points given for HLA matching are for 0 and 1 HLA-DR antigen mismatches 7 (DRMM), which receive 2 and 1 points, respectively. Thus, we investigated the potential for Tregitope-mediated antigen-specific tolerance induction via searching for an HLA-DR antigen matching effect on deceased donor (DD) kidney transplantation outcomes. During 2000–2013, a total of 133,235 patients who received a deceased donor kidney transplant alone were included in this study using the OPTN/UNOS data as of Sept. 30, 2014. In order to investigate HLA-DR antigen matching effect on graft survival, recipients who received a deceased donor kidney with 1 DRMM (n = 57,436) were divided into 2 groups: (1) Group I, HLA-DR10, 14, or 16 antigen match (n = 1,436); (2) Group II, no HLA-DR10, 14, or 16 antigen match (n = 56,000). For reference groups, 0 DRMM (n = 29,223) and 2 DRMM (n = 46,576) groups were included in the study. Stepwise decreases in graft survival rates were seen (Fig. 1). Group I showed the highest survival rates, followed by 0 DRMM (P = 0.146 vs Group I), Group II (P < 0.001 vs Group I), and 2 DRMM group (P < 0.001 vs Group I). After adjusting for confounders (such as donor, recipient, pre- and post-transplant risk factors, not shown here), Group I yielded significantly superior graft survival rates compared to Group II (P < 0.001). HLA-DR10, 14, or 16 matching, despite other donor HLA-DR antigen mismatches, was associated with graft survival superior to other HLA-DR matches. This effect could be associated with Tregitope-mediated antigen-specific tolerance induction, due to more efficient presentation of IgG-derived Tregitopes by matched HLA-DR10, 14, or 16 proteins.Download : Download full-size image