Immunogenic human leukocyte antigen class II antigens on human cardiac valves induce specific alloantibodies

Background. The kinetics of panel reactive antibodies (PRA) and incidence of antibodies directed against human leukocyte antigen (HLA) class II were studied in patients who received a cryopreserved cardiac valve allograft. Methods. A complement-dependent microlymphocytotoxicity test was used to determine the percentage of panel reactive antibodies. Anti–HLA class II antibodies were measured by two-color fluorescence assays. Results. The panel reactive antibodies became positive in 25 (78%) of 32 recipients between 1 and 16 months after implantation. Antibodies against HLA class II antigens were detected in 11 (37%) of 30 patients. In 9 (82%) of 11 cases these antibodies were donor specific. The induction of antibodies against donor HLA class II antigens suggests that intact HLA class II antigens are expressed by viable cells within the graft. Dithiothreitol analysis showed that the antibodies were of the immunoglobulin G type. Apparently, the HLA class II antigens are expressed in an immunogeneic way, as activation of specific T-helper cells is essential for the switch from immunoglobulin M to immunoglobulin G antibodies. Conclusions. Allogeneic valve transplantation is associated with the production of donor-specific anti–HLA class I and II antibodies that could contribute to graft failure. This possibly detrimental effect might be prevented by cross matching in sensitized patients.