INFLUENCE OF HLA-DR PHENOTYPE ON TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION IN RENAL-TRANSPLANT RECIPIENTS

In healthy subjects, previous studies have demonstrated a great interi ndividual variability in the ability for tumor necrosis factor-alpha ( TNF-alpha) production. The gene for TNF-alpha is closely linked to and located in the major histocompatibility complex (MHC) and it has been suggested that these interindividual differences may be HLA related. Since TNF-alpha is likely to be an important mediator in renal allogra ft rejection, we investigated the role of HLA antigens on TNF-alpha pr oduction rates by peripheral blood mononuclear cells (PBMC) from renal transplant recipients during stable graft function. HLA-DR2-positive recipients showed significantly lower spontaneous TNF-alpha production than DR2-negative patients (p < 0.001). Upon stimulation with OKT3, H LA-DR2-positive patients also showed significantly lower TNF-alpha pro duction than DR2-negative subjects (p < 0.001). HLA-DR3-positive recip ients, however, showed significantly higher spontaneous TNF-alpha prod uction than DR3-negative individuals (p < 0.05). These results suggest that differences in TNF-alpha production, both spontaneous and induce d, may be due to the expression of certain DR allotypes.