Donor-specific antibodies against HLA-C, HLA-DP and HLA-DQ and their implications in kidney transplantation.

HLA-C, HLA-DP and HLA-DQ are thought to be benign due to low expression and few initial negative studies. Historically, most allocation programs used HLA-A, HLA-B and HLA-DR antigens for matching. With the advent and use of single-bead antigen assays, more was learned about donor-specific antibodies (DSAs) against these antigens. Interest in these antigens and antibodies grew when cases of acute antibody-mediated rejection (AMR), mixed rejections, chronic AMR, and reduced graft survival were reported with DSAs against these antigens. Although the deleterious effects of these DSAs are more pronounced in retransplants, harmful effects have also been observed in first-time recipients. DSAs against each of these antigens can trigger rejection alone. Their combination with DSAs against HLA-A, HLA-B and HLA-DR can cause more damage. It has been shown that strategies that reduce mismatches for these antigen lead to fewer rejections and better graft survival. There is a need for greater consensus on the universal typing of these antigens prior to transplantation for better patient and graft outcomes. This review focuses on the interaction of these antigens with lymphocytes and killer immunoglobulin receptors, arguments for not typing them, detailed analyses of the literature about their harmful effects, potential strategies moving forward, and recommendations for the future.