HLA DNA typing and transplantation

PCR-based methods of HLA class I and class II typing have been developed that are simple, rapid, highly informative, and automatable and can be carried out at either intermediate or high levels of allelic resolution in a clinical diagnostic setting as well as for research studies. For solid organ transplants, the data indicate that the degree of HLA matching, in terms of the number of mismatched A, B, and DR antigens, significantly affects the survival of kidney grafts, for both cadaveric and living unrelated donors, even with the most recent protocols of immunosuppresion. The degree of HLA matching also significantly affects the survival of heart transplants but not of liver transplants. For bone marrow transplants, where the HLA typing was carried out at the allele level, the comparison of DNA-matched with DNA-mismatched among serologically matched donor and recipient pairs indicates that both graft rejection and graft versus host disease occur more frequently in allele-mismatched transplants. Acute graft versus host disease is increased with recipient disparity for one DR or DQ allele or for two or more class I alleles. Bone marrow graft rejection was associated with donor disparity for two or more class I alleles. It is likely that the effect of mismatching on these various clinical outcomes will depend on the specific HLA alleles that differ between the donor and recipient. The increased use of DNA HLA typing in transplantation should help define the "rules" that govern the clinical outcomes of mismatched transplants and allow the identification of "permissible" (relatively well-tolerated) mismatches.