Anti-phospholipid antibodies contribute to arteriosclerosis in patients with systemic lupus erythematosus through induction of tissue factor expression and cytokine production from peripheral blood mononuclear cells

作者：Motoki Yukari; Nojima Junzo^*; Yanagihara Masashi; Tsuneoka Hidehiro; Matsui Tomohiro; Yamamoto Misa; Ichihara Kiyoshi

来源：Thrombosis Research, 2012, 130(4): 667-673.

DOI：10.1016/j.thromres.2011.11.048

• systemic lupus erythematosus
• anti-phospholipid antibodies
• tissue factor
• arteriosclerosis
• monocytes
• cytokine

Introduction: In systemic lupus erythematosus (SLE) patients, the prevalence of arteriosclerosis obliterans (ASO) is high despite a lack of common risk factors for ASO. The main objective of this study was to investigate a possible direct role of anti-phospholipid antibodies (aPLs), which are frequently detected in SLE patients, in the pathogenesis of ASO. %26lt;br%26gt;Materials and Methods: We examined tissue factor (TF) expression on the monocyte surface by flow cytometric analysis in 89 SLE patients with or without ASO and/or aPLs and studied the in vitro effect of purified IgG fractions from plasma of SLE patients or normal healthy volunteers (aPLs(+) IgG, n = 8; aPLs(-) IgG, n = 6; Normal IgG, n = 6) on the expression of TF and production of TNF-alpha and IL-1 beta in healthy peripheral blood mononuclear cells (PBMCs) or isolated monocytes. %26lt;br%26gt;Results: We confirmed that high expression of monocyte TF was strongly associated with the prevalence of ASO and the presence of aPLs. Treatments of PBMCs with aPLs(-) IgG or normal IgG did not significantly increase expression of TF, TNF-alpha, and IL-1 beta messenger RNA (mRNA) and the production of TNF-alpha and IL-1 beta. However, stimulation of PBMCs with aPLs(+) IgG caused significant increase in expression of TF, TNF-alpha, and IL-1 beta mRNA. Moreover, aPLs(+) IgG stimulated PBMCs and significantly enhanced the production of TNF-alpha and IL-1 beta. %26lt;br%26gt;Conclusion: These results suggest that IgG-aPLs cause persistently high TF expression and inflammatory cytokine production by interacting with peripheral blood monocytes and lymphocytes, which may be an important mechanism in the pathogenesis of ASO peculiar to SLE patients.

• 出版日期2012-10