Acquired activated protein C resistance is associated with IgG antibodies to protein S in patients with systemic lupus erythematosus.

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.