Association between the prevalence of antibodies to beta(2)-glycoprotein I, prothrombin, protein C, protein S, and annexin V in patients with systemic lupus erythematosus and thrombotic and thrombocytopenic complications

Background: Anti-phospholipid (aPL) antibodies (Abs) frequently found in th e plasma of patients with systemic lupus erythematosus (SLE) have been asso ciated with thrombotic complications. Our aim was to clarify the roles in t hrombosis of aPL Abs that react with complexes of phospholipids and plasma proteins such as beta (2)-glycoprotein I (beta (2)-GPI), prothrombin, prote in C, protein S, and annexin V. Methods: We determined the prevalence of aPL Abs to various phospholipid-bi nding plasma proteins in SLE patients with arterial thrombosis (30 cases), venous thrombosis (19 cases), thrombocytopenia (14 cases), fetal loss (14 c ases), and patients without complications (91 cases). The aPL Abs were meas ured by an ELISA system in which human plasma proteins (beta (2)-GPI, proth rombin, protein C, protein S, and annexin V) were immobilized on gamma -irr adiated or plain polystyrene plates. Results: All types of aPL Abs were frequently observed in the patients with SLE when gamma -irradiated polystyrene plates were used (51 of 168 cases p ositive for anti-beta (2)-GPI, 94 of 168 cases positive for anti-prothrombi n, 36 of 168 cases positive for anti-protein C, 47 of 168 cases positive fo r anti-protein S, and 50 of 168 cases positive for anti-annexin V), whereas no Abs to these plasma proteins were detected when plain polystyrene plate s were used. Multivariate analysis confirmed that both anti-beta (2)-GPI an d anti-prothrombin Abs were significant risk factors for arterial thrombosi s [odds ratios (ORs), 8.8 and 14.5, respectively; 95% confidence intervals (CIs), 3.2-25 and 1.8-116, respectively] but not for venous thrombosis. The presence of anti-protein S Abs was a significant risk factor for venous th rombosis (OR, 30.4; CI, 3.3-281) but not for arterial thrombosis. The only significant risk factor for fetal loss was the presence of anti-annexin V A bs (OR, 5.9; CI, 1.4-14.8). Conclusions: Patients with SLE frequently have some aPL Abs to beta (2)-GPI , prothrombin, protein C, protein S, and annexin V. Thrombotic complication s in SLE may depend on the antigenic specificities of these Abs, alone or i n combination. (C) 2001 American Association for Clinical Chemistry.