A future for HLA matching in clinical transplantation

The arguments for and against minimizing HLA antigen mismatching in clinical transplantation have been debated for the past 30 years (Terasaki & Cecka, 1994), but at least two major kidney exchange programmes (EURO- and UK-Transplant), with waiting lists totalling 17 thousand patients, prioritize the least HLA mismatched recipients. In the USA, in the United Network for Organ Sharing (UNOS) zero HLA-A,-B, DR mismatch for exchange of kidneys is mandatory. There is now a clear understanding of the in vivo function of HLA molecules, which have a central role in antigen presentation to T cells and thus initiate the immune response both in the normal individual and in transplant recipients. In the latter case, direct recognition of foreign HLA molecules by recipient T cells is also possible (Shoskes & Wood, 1994). With such a clear understanding of the central functional role for HLA in the immune response, it is not surprising that reports of increased kidney transplant survival correlate with reduced HLA mismatching, and it is of concern that some centres choose to allocate kidneys for transplant ignoring HLA. Reports of benefits of minimizing HLA mismatching in heart (Smith et al., 1995) and lung (Iwaki et al., 1993) transplantation are limited to retrospective studies, and no centre has claimed to allocate these organs taking HLA mismatch into account. Consequently, HLA mismatched thoracic organ transplants predominate, but nevertheless recipients of completely mismatched organs have decreased survivals (Opelz & Wujciak, 1994) and more rejection (Baan et al., 1991; Jarcho et al., 1994). Since transplantation of hearts and lungs is essentially only effective on one occasion, all effort should be made to maximize survival and incorporation of HLA mismatches in allocation criteria for these organs is now overdue (Disesa et al., 1990; Morris, 1994). In this brief review we choose not to cover the extensive literature on the role of HLA mismatching in organ transplantation, but consider the field at the present time with particular emphasis on realistic, practical application of HLA typing to the clinical situation and, in particular, the development of allocation procedures that will best suit the needs of individual patients.