Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome.

BACKGROUND: This study aimed to determine whether the production, in renal transplant recipients, of antibodies directed against donor HLA mismatches is predictive of transplant failure. METHODS: The failure study group comprised 112 adult recipients of primary renal transplants who had re-entered the transplant waiting list after failure of the first graft. A control group of 123 recipients with functioning transplants was selected from transplantations performed during the same time period, in which patients had equivalent HLA matching and immunosuppression and a minimum of 5 years of follow-up. Sera taken before transplantation and at 1, 3, and 6 months and annually after transplantation were tested by enzyme-linked immunoabsorbent assay (ELISA) for the presence of HLA class I- and class II-specific antibodies. Antibody specificity was defined by a combination of cytotoxicity, ELISA, and flow cytometry techniques to determine whether the antibodies were directed against donor mismatches. RESULTS: All recipients were negative for donor HLA-specific antibodies before transplantation. After transplantation, 57 (50.9%) of the 112 patients in the failure group produced donor HLA-specific antibodies compared with 2 (1.6%) of the 123 controls (P<0.0001; odds ratio [OR]=64.98; confidence interval [CI], 14.78-399.51). For 60% of the donor-specific antibody-positive patients, antibodies were detected before transplant failure. In 17 cases, these were class I specific; in 14 cases, class II specific; and in 3 cases, specific for both class I and II. CONCLUSIONS: This study has demonstrated that the production of posttransplantation antibodies directed against donor HLA-A, -B, -Cw, -DR, and -DQ mismatches are all strongly predictive of transplant failure.

The role of HLA-specific antibodies in kidney transplant rejection: published studies and local data.

The post-transplantation production of antibodies directed against donor HLA class I and class II mismatches has been shown to be associated with transplant rejection. Recipient sensitization against donor HLA plays a key role in transplant rejection; this risk is best minimized by efficient pre-transplant antibody detection and definition, effective pre-allocation cross-matching, and minimization of HLA mismatches between donor and recipient. The term "PRA" is of little value. Identification of the HLA specificity to which an antibody is directed is essential and now possible using contemporary methodology. It is now recognized that antibody-mediated rejection should be diagnosed on the basis of allograft dysfunction, characteristic features of histology, C4d immunohistology, and the presence of donor-specific antibodies. HLA-DP is becoming recognized as a "transplantation antigen." For the future, the repertoire of a histocompatibility laboratory must expand to include typing organ transplant recipients and donors for HLA-DP and also the definition of antibodies to DP. Antibodies to non-HLA targets should be an important consideration when assessing factors that influence transplant outcome.