Effect of Bw4 and Bw6 epitope mismatches on antibody production, acute andchronic rejection, and graft survival in renal allografts

Background. Highly sensitized patients often have antibodies directed again st the HLA Bw4 and Bw6 epitopes. Because of the high frequency of these epi topes, when present, these antibodies result in a high incidence of positiv e cross-matches. We sought to determine whether antibodies specific for Bw4 or Bw6 affected renal allograft outcome. Methods. The effect of mismatches for the HILA class I public epitopes, Bw4 and Bw6, was examined in 72 recipients of one haplotype matched recipients of living, related donor renal allografts selected to control! for degree of HILA mismatch. Analysis of the production of HILA-specific antibody was performed for 180 recipients of failed cadaveric allografts by complement-d ependent cytotoxicity tests and by an enzyme-linked immunoadsorbent assay ( ELISA). Results. No significant difference was observed in the incidence of acute r ejection, number of rejection episodes or 1-year allograft survival among B w4/6 matched versus mismatched recipients of one haplotype matched allograf ts. Additionally, no significant difference in the development of chronic a llograft nephropathy was noted among 56 recipients followed long-term (grea ter than or equal to3 years). In the recipients of failed cadaveric transpl ants, Bw4/6 mismatching was associated with the frequency and magnitude of production of HLA-specific antibody. However, the panel reactive antibodies correlated with the number of HLA-A and -B mismatches, and there was no ad ditional impact of Bw4/6 mismatching. IgG, HILA-specific antibodies were fo und to be significantly increased among patients homozygous for Bw4 or Bw6, whether or not there was a Bw4/6 mismatch. Conclusions. Mismatching for Bw4 or Bw6 does not confer any independent, in creased risk for humoral sensitization or renal allograft failure.