Repeat donor HLA-DR mismatches in renal transplantation: Is the increased failure rate caused by noncytotoxic HLA-DR alloantibodies?

Introduction. Data from the UCLA/UNOS and Collaborative Transplant Studies Registries indicate that mismatched HLA-DR alloantigens expressed on a former donor renal allograft should not be repeated because of significantly poorer long-term survival. Methods. Retransplant candidates waiting for another renal allograft were screened for ELLA class II alloantibodies (aAb) using direct complement-dependent cytotoxicity and several sensitive aAb binding assays. Results. When screened by complement-dependent cytotoxicity, 46% of the patients were aAb negative. In contrast, using aAb binding assays, 90% of the patients had HLA-DR aAb specific for previous HLA-DR allograft mismatches. Most important, no directly cytotoxic HLA-DR antibody was detected in 9 of 27 patients. Conclusion. Our studies suggest that crossing the same HLA-DR mismatch in a subsequent transplant may result in poorer survival due to underlying donor-specific HLA-DR aAb. If confirmed in a retrospective study of retransplant patients, B cell donor crossmatches using antiglobulin complement-dependent cytotoxicity or flow cytometry would appear essential if this barrier were to be crossed.