Abnormal Fas/FasL and caspase-3-mediated apoptotic signaling pathways of T lymphocyte subset in patients with systemic lupus erythematosus

Objectives. To explore the relationships between Fas-FasL-mediated signaling pathway and apoptosis disturbance of T lymphocyte subset in patients with SLE. Methods: Flow cytometry was used to determine the percentage of apoptotic lymphocytes and necrotic lymphocytes by AnnexinV-FITC/PI double staining. Cell surface expression rates of Fas, FasL, and intracellular expression rates of activated caspase-3 were evaluated by two-color flow cytometry analysis in peripheral T lymphocyte subsets of LE patients with inactive disease (n = 22) and with active disease (n = 17). The serum concentration of anti-nucleosome antibodies in SLE patients were assayed by ELISA immunoassay methods. Health volunteers (n = 13) served as controls. Results: The percentage of early apoptotic cells was enhanced inpatients with active disease (P=0.001, vs. control) and inpatients with inactive disease (P = 0.004, vs. control). Compared with health control, the percentage of necrotic cells was significant higher in patients with active disease (P=0.001). The percentages of CD4(+)T cells expressing Fas (P=0.023, vs. control) and FasL (P=0.001, vs. control) were increased in patients with active disease. But there were no obvious differences of expression rates of Fas and FasL on T cell subset between two disease groups (P > 0.05). In patients with active disease the percentage of CD4(+)T cells or CD8(+)T cells expressing intracellular activated caspase-3 significantly increased compared to inactive disease patients (P=0.018, P=0.027, respectively) and health controls (P=0.001, P=0.001, respectively). The serum concentration of anti-nucleosome antibodies was strikingly higher in patients with active disease (P=0.002, vs. patients with inactive disease; P=0.001, vs. control, respectively), however, the serum concentration of anti-nucleosome antibodies was not obviously different between patients with inactive disease and health control group (P = 0.473). The percentage of apoptotic cells correlated with the serum concentration of anti-nucleosome antibodies in SLE patients (r,=0.350,P=0.031). Conclusions: Apoptosis of T lymphocyte subset in SLE patients increases. CD4(+)T cells are a state of active apoptosis. Fas/FasL-mediated apoptotic pathways are especially important for CD4(+)T cells undergoing apoptosis in SLE patients with active disease. Increased Fas expression results in a higher susceptibility to Fas-mediated apoptosis, which contributes to the increased levels of intracellular activated caspase-3 and accelerates apoptosis of T lymphocytes. The degree of lymphocytic apoptosis disturbance correlates with the level of anti-nucleosome antibodies in the circulation. Acceleration of lymphocytic apoptosis plays important roles in immune pathologic injury and immune regulation dysfunction. (c) 2006 Elsevier Inc. All rights reserved.