Identification of the antibodies involved in B-cell crossmatch positivity in renal transplantation

The significance of a positive B-cell crossmatch (BCM) in kidney transplantation has always been controversial in the evaluation of its implications on graft survival and specificity of the antibodies involved. We have investigated the sera of 62 recipients of a kidney allograft transplanted across a positive BCM (T negative) for the presence of autoantibodies and anti-human leukocyte antigen (HLA) class I and II antibodies, using a combination of lymphocytotoxicity, enzyme-linked immunosorbent assay (ELISA), and flow cytometry tests. The controls were the 930 patients transplanted over the same period of time with a negative T and BCM. Autoantibodies were detected in 16%, and donor specific anti-HLA class II antibodies, mainly DQ, in 23% of the patients. None had antibodies against donor HLA class I. The target of the antibodies was not identified in 61%. Graft survival was comparable in the controls and in the +BCM patients, with nondonor-specific HLA reactivity. Patients with donor-specific anti-HLA class II antibodies had lower early graft survival and a higher incidence of vascular rejection. However, long-term allograft survival was similar to that of the other groups. These data suggest that in 77% of the patients, BCM positivity was not related with anti-HLA antibodies, and, in this case, graft survival was similar to that of the -BCM controls. In a minority of patients, anti-HLA class II antibodies were responsible for the +BCM, and their presence was associated with lower early, but not long-term, graft survival. Consequently, a +BCM should not systematically contraindicate kidney transplantation.