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

Abstract

BackgroundBoth 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.MethodsLeukocyte 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.ResultsExcept 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).ConclusionsLeukocyte 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.

Suppression of autoreactive T and B lymphocytes by anti-annexin A1 antibody in a humanized NSG murine model of systemic lupus erythematosus

“…Similar results were observed in pristane‐induced murine lupus using the same antibody, suggesting shared mechanisms of T cell activity regulation through the ANX A1–FPR2 signalling pathway . The accumulated data suggest a more complex relation between ANX A1, the monoclonal antibody and apoptosis, respectively, rather than a simple pro‐ or anti‐apoptotic effect .…”

Attenuated phagocytosis of secondary necrotic neutrophils by macrophages in aged and SMP30 knockout mice

“…We and other researchers had previously shown that secondary necrotic cells generated in vivo caused strong inflammatory responses and many diseases; for example, autoimmune disease, such as systematic lupus erythematosus . It has been known that the function of the immune system decreases with age, leading to increased susceptibility of the elderly to infections by viruses and bacteria .…”

“…Secondary necrotic cells also cause chronic inflammatory diseases, because Su et al . previously reported that repeated injection of secondary necrotic cells caused autoimmune diseases, such as systematic lupus erythematosus …”

“…[5][6][7][8][9][10][11] Secondary necrotic cells also cause chronic inflammatory diseases, because Su et al previously reported that repeated injection of secondary necrotic cells caused autoimmune diseases, such as systematic lupus erythematosus. 12 In contrast, the function of the immune system decreases with age, leading to increased susceptibility of the elderly to infections by viruses and bacteria. 13,14 Previous studies showed that virus-specific T-cell responses are decreased in aged animals, and that the production of inflammatory mediators, such as tumor necrosis factor-α and nitric oxide, and dangerassociated molecular patterns released from secondary necrotic cells, such as high mobility group box-1, was increased in aged mice when lipopolysaccharide was injected into aged animals.…”

Influenza A (H1N1) virus infection triggers severe pulmonary inflammation in lupus-prone mice following viral clearance

“…Likewise, in SLE, increased apoptosis and defects in apoptotic clearance have been implicated in disease pathogenesis [46, 47]. However, failure to remove autoreactive cells in SLE by activation induced apoptosis can also contribute to autoimmune disease symptoms [35].…”