Autoantibodies to β₂-glycoprotein I in systemic lupus erythematosus and primary antiphospholipid antibody syndrome: Clinical correlations in comparison with other antiphospholipid antibody tests

Objective. To examine relationships between anti-β₂-glycoprotein (β₂-GPI) antibodies and other antiphospholipid antibody (aPL) tests (aPL ELISA and the lupus anticoagulant or LAC) and the associations of each of these aPL tests with individual clinical manifestations of the antiphospholipid antibody syndrome (APS). Methods. IgG and IgM anti-β₂-GPI antibodies were determined by ELISA in 281 patients with SLE, primary APS, or other connective tissue diseases. Frequencies, sensitivities, specificities, and predictive values and correlations of anti-β₂-GPI were compared to the aPL ELISA (IgG and IgM) and LAC for individual (and combined) features of APS. Results. Among 139 patients with positive aPL ELISA and/or LAC tests, 57 (41%) had anti-β₂-GPI antibodies (IgG and/or IgM) compared to 11% of patients with SLE negative for these tests (p = 0.00001). In 130 patients with APS, anti-β₂-GPI occurred in 42% and tended to be more specific but less sensitive than the aPL ELISA or LAC. When all 3 aPL tests were combined, the best sensitivities and negative predictive values were achieved; however, specificity and positive predictive values remained low. Anti-β₂-GPI antibodies occurred more frequently in primary APS (58%) vs secondary antiphospholipid syndromes (33%) (p = 0.008, OR = 2.9). Among 79 patients with SLE negative by both aPL ELISA and LAC, 9 (11%) were positive for anti- β₂-GPI, 7 of whom had clinical features consistent with APS (representing 5% of all with APS). Stepwise multiple logistic regression analysis revealed β₂-GPI to be most strongly associated with neurological syndromes other than stroke, deep venous thrombosis, and recurrent fetal loss, while LAC was most strongly correlated with stroke and thrombocytopenia. IgM aPL antibodies also were independently associated with neurological syndromes and recurrent fetal loss. Conclusion. Testing for β₂-GPI antibodies may be clinically useful in the diagnosis of APS but cannot supplant other aPL ELISA or LAC. Multivariate analyses suggest that anti-β₂-GPI antibodies may play a more central role in certain clinical manifestations of APS than antibodies detected by the aPL ELISA or LAC.