title: Acquired activated protein C resistance is associated with IgG antibodies to protein S in patients with systemic lupus erythematosus.
abstract: The objective of this study was to clarify the roles of anti-phospholipid antibodies (aPLs) in the pathogenesis of acquired activated protein C resistance (APC-R) in patients with systemic lupus erythematosus (SLE). We examined several aPLs levels (lupus anticoagulant, anti-cardiolipin antibodies, anti-beta2-glycoprotein I antibodies, anti-protein C antibodies, and anti-protein S antibodies), the APC-R test, and the factor V Leiden test in 85 SLE patients. Acquired APC-R, which was not found in any patient with the factor V Leiden mutation, was present in 26 (30.6%) of 85 patients, and confirmed that acquired APC-R was a significant risk factor for thromboembolic complications [odd ratio (OR), 3.36; 95% confidence interval (CI), 1.24-9.11]. Multivariate logistic analysis revealed that both LA and anti-PS strongly associated with the presence of APC-R, and that the correlation between anti-PS and APC-R was much stronger (OR, 46.7; 95%CI, 6.99-311) than that between LA and APC-R (OR, 11.3; 95%CI, 2.26-57.0). Furthermore, the mean value of APC sensitivity ratios was significantly lower in SLE patients with anti-PS (mean +/- SD, 1.68 +/- 0.37, p < 0.0001) than in those without anti-PS (2.23 +/- 0.40). These results suggest that acquired APC-R is most strongly attributable to functional interference of the APC pathway by anti-PS, which contribute to risk of thromboembolic complications.
authors.affiliation: Department of Laboratory Science, Faculty of Health Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan. nojima-j@yamaguchi-u.ac.jp
authors.forename: Junzo
authors.initials: J
authors.lastname: Nojima
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Iwatani
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ichihara
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Tsuneoka
authors.forename: Toshizo
authors.initials: T
authors.lastname: Ishikawa
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagihara
authors.forename: Toru
authors.initials: T
authors.lastname: Takano
authors.forename: Yoh
authors.initials: Y
authors.lastname: Hidaka
mesh_terms: D020016:Activated Protein C Resistance / Q000150:complications* / Q000209:etiology* / Q000276:immunology; D000328:Adult; D000368:Aged; D017152:Antibodies, Antiphospholipid / Q000032:analysis; D016022:Case-Control Studies; D016001:Confidence Intervals; D005165:Factor V; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000150:complications*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D017293:Protein S / Q000032:analysis*; D012307:Risk Factors; D013923:Thromboembolism / Q000150:complications / Q000209:etiology
chemical_list: D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D017293:Protein S; C095381:factor V Leiden; D005165:Factor V