THE ROLE OF HLA MATCHING IN TRANSPLANTATION

All viable human tissues transplanted from one individual to another are at risk of rejection. The extent of risk depends on the donor HLA-host T cell receptor disparity. Such disparity is now known to involve genetic products coded by both HLA and non-HLA genes. T cells responses to mismatches on transplants are graded: the greater the mismatch the greater the number of clones of T cells responding. Consequently, the more severe the rejection process. Global statistics support this view in that cumulative mismatches at HLA are associated with poorer graft survival. However such studies also suggest that mismatches at different HLA loci vary in potency. The strength of mismatch seems to increase from HLA-A, the weakest, through HLA-B to HLA-DR, the most potent. Analysis of clinical results suggests that the risk associated with HLA mismatches in kidney transplantation dwindles after the first five months post-transplant. Although graft losses tend to occur sporadically thereafter, no major risk associated with HLA mismatches can be discerned. Whether this dwindling impact of HLA mismatches with time post-transplant is a general phenomenon applicable to all transplants, or whether it suggests some form of adaptation of host to graft in kidney transplant recipients alone is a subject for further exploration. Tissues vary widely in their susceptibility to rejection through HLA mismatches. Thus unrelated donor marrow transplantation is exquisitely sensitive to even a single mismatch at the HLA-C locus for example, whereas cornea in 90% of recipients appears to be relatively resistant. In both cornea and unrelated marrow transplantation, immunosuppression can be safely withdrawn post-transplant once the inflammatory responses have settled down. In all other types of transplant including kidney, heart, lung and liver, immunosuppression for the lifetime of the recipient is essential to suppress rejection. This suggests that the adaptation process differs with different organs and could if explored on a comparative basis enlighten us as to how to develop future clinical strategies.