Assessment of the independent associations of IgG, IgM and IgA isotypes of anticardiolipin with thrombosis in SLE

Objective: The Sydney classification criteria for antiphospholipid syndrome include lupus anticoagulant or moderate-to-high titre anticardiolipin IgG or IgM. We explored the association of all anticardiolipin isotypes, lupus anticoagulant and the combination with venous and arterial thrombosis. Methods: Patients with systemic lupus erythematosus (SLE) in a large clinical cohort seen quarterly were repeatedly tested by protocol for anticardiolipin antibodies and lupus anticoagulant. Subgroups of patients were defined based on the geometric mean titres of IgG, IgM, IgA anticardiolipin and lupus anticoagulant expressed in dilute Russell's viper venom time (RVVT) seconds for each patient across all cohort visits. These subgroups were compared with respect rates of thrombosis since diagnosis with SLE. Rate ratios were estimated using Cox Proportional Hazards models. Results: Of the 1390 cohort members included, there were 284 thrombotic events observed over 17 025 person-years since diagnosis for a rate of 1.7 events per 100 person-years. Those with a geometric mean titre of IgG anticardiolipin >20 had a significantly elevated rate of thromboses (rate ratio 1.8, p=0.0052), whereas there was no evidence of an association between thromboses and elevated IgM geometric mean (rate ratio 1.2, p=0.40). There were relatively few cohort members with elevated IgA geometric mean but the rate of thromboses in that group was elevated (rate ratio 1.7, p=0.23). The associations between anticardiolipin antibodies and thromboses were strongest when considering venous thromboses. Those with two or more elevated anticardiolipin isotypes or those with both IgG anticardiolipin and RVVT did not appear at higher risk than those with a single elevated marker. Conclusion: This study supports previous observations that IgG anticardiolipin and lupus anticoagulant are associated with higher rates of thromboses. Our power to study IgA anticardiolipin was limited due to small number of patients with elevated IgA.