Do Elevated Levels of Serum-Soluble Fas Contribute to the Persistence of Activated Lymphocytes in Systemic Lupus Erythematosus?

Abstract

Systemic lupus erythematosus (SLE) is characterized by generalized immune activation. Part of this might be explained by a decreased rate of apoptosis, possibly related to elevated levels of soluble Fas (sFas) which can inhibit Fas mediated apoptosis of lymphocytes. In order to substantiate the relation between levels of sFas and lymphocyte activation in SLE we monitored sFas levels, lymphocyte activation and disease activity in 25 SLE patients. SLEDAI scores were registered and sera were assayed for sFas levels by an enzyme-linked immunosorbent assay. Flow cytometry was used to monitor the state of activation of lymphocyte subsets. Eighteen healthy, age-matched volunteers served as controls. Soluble Fas levels were elevated in SLE patients (n=25) compared to healthy controls (n=18,P=0.002). Soluble Fas levels correlated with SLEDAI scores (r=0.45,P=0.02). Levels of sFas correlated with the percentages of activated B cells defined as CD20⁺CD38⁺cells (r=0.47,P=0.009). Percentages of CD20⁺CD38⁺cells were increased in quiescent SLE compared to healthy controls (P=0.003). The expression of activation markers on CD4⁺T lymphocytes (IL-2R,P=0.04; HLA-DR,P=0.01) and CD8⁺T lymphocytes (HLA-DR,P=0.007) was also increased in quiescent SLE compared to controls. Activation markers on all lymphocyte subsets tended to increase further during disease activity. No correlation was observed between percentages of activated T lymphocyte subsets and levels of sFas. In conclusion, soluble Fas levels are increased in SLE patients and correlate with disease activity as measured by the SLEDAI score and B and T cell subsets are activated even during quiescent SLE. Serum levels of sFas correlate with percentages of activated B cells but not with that of activated T cells.