HLA matching: identification of permissible HLA mismatches

Previous studies of mismatches for a single HLA antigen in kidney transplants have not demonstrated that any single HLA antigen was more immunogenic than another. Here we show that certain mismatched antigens are "permissible" to recipients of certain types and not to others. In this retrospective study of 1,273 living-donor kidney transplants, a mismatch for 27 different, single A,B,DR antigens was evaluated with respect to recipients of various types. Various combinations of donor/recipient incompatibilities were then classified as "permissible" or immunogenic, depending upon the fate of the transplant. This list was then evaluated with 1,905 patients who received cadaver-donor transplants mismatched for a single A,B,DR antigen. Cadaver-donor kidney transplants judged to have received a permissible mismatch in the A, B, or DR loci had graft survival rates equivalent to zero-A,B,DR-mismatched grafts. Among 425 patients with one-A,B,DR-permissible mismatches, one-year graft survival was 89% with a 14.1-year half-life, compared with 966 one-A,B,DR-mismatched grafts with an 89% one-year survival and an 18-year half-life. Based upon these results, we recommend the initiation of one permissible A,B,DR-mismatched transplants for national sharing. This will result in potentially 60% of shared transplants having high long-term graft survival rates.