THE APOPTOSIS-1 FAS PROTEIN IN HUMAN SYSTEMIC LUPUS-ERYTHEMATOSUS

Three independent mutations involving the apoptosis-1 (APO-1)/Fas rece ptor or its putative ligand have led to lupuslike diseases associated with lymphadenopathy in different strains of mice. To determine whethe r humans with SLE also have a defect in this apoptosis pathway, we ana lyzed the expression of APO-1 on freshly isolated blood mononuclear ce lls and on lymphocytes activated in vitro using flow cytometry and the monoclonal antibody anti-APO-1. Significantly higher levels of APO-1 expression were detected on freshly isolated peripheral B cells and bo th CD4(+) and CD8(+) T lymphocyte populations obtained from lupus pati ents when compared with normal controls (P < 0.001). Almost 90% of the cells that stained positive for APO-1 also expressed the CD29 antigen , suggesting that APO-1 was upregulated after lymphocyte activation in vivo. No defect in APO-1 regulation was detected after activation of SLE T (with anti-CD3) or B (with Staphylococcus aureus Cowan 1) lympho cytes in the presence of IL-2 in vitro. Similarly, the anti-APO-1 anti body induced apoptosis in 74+/-5% of activated SLE T cells in vitro co mpared with 79+/-6% of the normal controls (P > 0.05). These results r eveal that, while APO-1/Fas may play an important role in the regulati on of lymphocyte survival in SLE, no consistent defect in the expressi on or function of the receptor could be detected in these studies.