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

Background. The kinetics of panel reactive antibodies (PRA) and incidence o f antibodies directed against human leukocyte antigen (HLA) class II were s tudied in patients who received a cryopreserved cardiac valve allograft. Methods. A complement-dependent microlymyhocytoxicity test was used to dete rmine the percentage of panel reactive antibodies. Anti-HLA class II antibo dies were measured by two-color fluorescence assays. Results. The panel reactive antibodies became positive in 25 (78%) of 32 re cipients 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 antig ens 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 activati on of specific T-helper cells is essential for the switch from immunoglobul in M to immunoglobulin G antibodies. Conclusions. Allogeneic valve transplantation is associated with the produc tion of donor-specific anti-HLA class I and II antibodies that could contri bute to graft failure. This possibly detrimental effect might be prevented by cross matching in sensitized patients. (C) 1998 by The Society of Thorac ic Surgeons.