title: 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.
abstract: BACKGROUND
  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.
  
  
  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-α and IL-1β in healthy peripheral blood mononuclear cells (PBMCs) or isolated monocytes.
  
  
  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-α, and IL-1β messenger RNA (mRNA) and the production of TNF-α and IL-1β. However, stimulation of PBMCs with aPLs(+) IgG caused significant increase in expression of TF, TNF-α, and IL-1β mRNA. Moreover, aPLs(+) IgG stimulated PBMCs and significantly enhanced the production of TNF-α and IL-1β.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Laboratory Science, Faculty of Health Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Motoki
authors.forename: Junzo
authors.initials: J
authors.lastname: Nojima
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagihara
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tsuneoka
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsui
authors.forename: Misa
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ichihara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000276:immunology*; D001162:Arteriosclerosis Obliterans / Q000209:etiology* / Q000235:genetics / Q000276:immunology*; D002648:Child; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D013925:Thromboplastin / Q000032:analysis / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D055815:Young Adult
chemical_list: D017152:Antibodies, Antiphospholipid; D016207:Cytokines; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin