ASSOCIATION BETWEEN SPECIFIC HLA COMBINATIONS AND PROBABILITY OF KIDNEY ALLOGRAFT LOSS - THE TABOO CONCEPT

Background HLA matching improves the outcome of cadaveric renal transp lantation. However, many allografts function well even in the presence of one or more HLA mismatches, which raises the question of whether s ome mismatches are better recognised by the recipient's immune system than others. We aimed to identify mismatched HLA donor-recipient combi nations that were associated with increased graft loss. Methods We sel ected 2877 first, unrelated renal transplants with a single HLA A, B, or DR mismatch, undertaken between 1982 and 1992, from the Eurotranspl ant database. To enhance statistical power the analysis was restricted to mismatches of an HLA antigen that occurred in 100 or more donors. 1342 transplants met this criterion and were grouped into a definition set (n=873) and a validation set (n=469). In the definition set, we s tudied further only those recipient HLA antigens that occurred in at l east 30 cases within each donor antigen mismatch subset. By a Cox prop ortional hazards model, donor-recipient combinations that led to signi ficantly higher graft loss than in the whole group were defined. Such combinations were classified as taboo; the remaining combinations were classified as indifferent. Findings 106 individual recipient antigens were found al least 30 times with a corresponding donor mismatch in t he definition set; 11 of the 106 had a significant effect on graft sur vival. Seven combinations were classified as taboo. Taboo combinations , confirmed as such in the validation set, were associated with graft survival of 81% at one year and 50% at 5 years, significantly lower th an the rates in the group with indifferent combinations (89% and 69%; p=0.04) or among 1190 recipients with no mismatches (89% and 72%; p=0. 03). The findings were substantiated by a multivariate analysis that i ncluded the effect of patient immunisation, cold ischaemia time, age, and sex. Interpretation Mismatched donor antigens are differentially r ecognised depending on the HLA phenotype of the recipient. The finding s may have important clinical consequences for graft survival after tr ansplantation.