The association among leukocyte apoptosis, autoantibodies and disease severity in systemic lupus erythematosus

Background: Both apoptosis and autoantibodies are important factors associated with disease activity in the pathogenesis of systemic lupus erythematosus (SLE). This study tested the hypothesis that increased leukocyte apoptosis is associated with elevated levels of autoantibodies and the disease activity of SLE. Methods: Leukocyte apoptosis was determined by flow cytometry, including annexin V, APO2.7, and 7-amino-actinomycin D (7-AAD) on each subtype of leukocyte in 23 patients with SLE. Leukocyte apoptosis was also evaluated in nine patients with Sjogren's syndrome (SJS) and in 20 volunteer subjects. Titers of common autoantibodies and the disease activity index (SLEDAI-2 k) of the SLE patients were also determined. Results: Except for annexin V and APO 2.7 of monocytes and late apoptosis (annexin V + 7-ADD) of lymphocytes, apoptosis in the total and in subsets of leukocytes were significantly higher in SLE patients than in controls (all p < 0.05, post hoc analysis). The mean percentage of late apoptosis of leukocytes (annexin V + 7-AAD) positively correlated with levels of anti-Ro52/60 (r = 0.513, p < 0.01), anti-La (r = 0.439, p = 0.04), and anti-Mi-2 (r = 0.492, p = 0.02), and inversely correlated with both C3 and C4 levels, although not statistically significant. The percentage of APO2.7 of CD19+ cells positively correlated with SLEDAI-2 K score (p = 0.01). Conclusions: Leukocyte apoptosis is significantly higher in patients with SLE and correlates well with the levels of several autoantibodies. The APO2.7 of B-lymphocyte (CD19+) cells positively correlates with the disease activity of SLE.