Increased costimulatory responses in African-American kidney allograft recipients

Background. The issue of racial differences in immune responses has been seldom investigated, despite the increased incidence of transplant rejection and inferior allograft outcomes in African-Americans (AA). We previously reported significantly increased expression of costimulatory molecules on peripheral blood cells from healthy adult AA compared with Caucasian (CS) volunteers. This report extends the study to pediatric kidney allograft recipients. Methods. Surface antigen expression by peripheral blood mononuclear cells (MNC) from AA and CS transplant patients was determined by flow cytometry, after staining with specific antibodies. In vitro proliferation, in a one-way mixed lymphocyte response (MLR), was measured after stimulation with allogenic irradiated mononuclear cells. The concentration of cyclosporine (CsA) achieving 50% inhibition (IC₅₀) of in vitro proliferative responses to PHA and OKT3 was calculated. Results. MNC from AA patients were shown to have significantly higher expression of CD80 (CS 5.2%±0.6, AA 9.6%±1.2, P<0.0001) than cells from CS patients. Additionally, the cells from AA transplant recipients proliferated significantly more in an MLR (stimulation index: CS8±2, AA 25±8, P<0.05), and the CsA IC₅₀ values, during proliferation to PHA and OKT3, were significantly higher in AA compared to CS patients. Conclusions. Although socioeconomic factors and therapeutic compliance are undoubtedly important issues in long-term allograft survival, our data suggest that AA patients mount more vigorous immune responses to antigens. The increased requirement for immunosuppression may be linked to racial variations in costimulatory molecule expression on antigen-presenting cells.