Role of Ia-Like Products of the Main Histocompatibility Complex in Conditioning Skin Allograft Survival in Man

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Abstract
This report correlates the survival time of 93 intrafamilial skin allografts performed under conditions of main histocompatibility complex (HLA) haploidentity with donor-recipient compatibility for products of the HLA-A, -B, -C, and -DR, as well as C3 proactivator, Glyoxalase I, and P loci located on the human 6th chromosome. Incompatibilities for HLA-A and -B (and to a lesser extent for HLA-C) and(or) for HLA-DR products exerted a strong influence upon the fate of skin allografts. When HLA-A and -B were considered alone, the most compatible group of grafts had a mean survival time of 15.8 d, as compared with 11.3 d for the most incompatible transplants. HLA-DR compatibility alone was associated with a mean survival time of 15.3 d, whereas HLA-DR-incompatible grafts had a mean survival time of 11.5 d. Incompatibilities for C3 proactivator, Glyoxalase I, and P did not have a significant effect upon graft survival. There was no evidence of an association between donor-recipient incompatibility at HLA-A, -B, or -C or at HLA-DR; such incompatibilities occurred independently of each other, in spite of the state of linkage disequilibrium known to exist between HLA-B and -DR. Incompatibilities for HLA-A, -B, and for HLA-DR exerted a potent additive effect upon graft survival. Skin grafts bearing one, two, or three incompatibilities had a mean survival time of 16.2, 13.7, and 10.7 d, respectively (P <0.0005). The results point to the important role played by the Ia-like products of the HLA complex (HLA-DR) in conditioning skin allograft survival in man. This consideration may be of direct relevance to the potential clinical usefulness of in vitro serological techniques for the detection of donor-recipient compatibility for HLA-DR.