AUTOANTIBODIES TO BETA(2)-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 beta(2)-glycoprotein (beta(2)-GPI) antibodies and other antiphospholipid antibody (aPL) tes ts (aPL ELISA and the lupus anticoagulant or LAG) and the associations of each of these aPL tests with individual clinical manifestations of the antiphospholipid antibody syndrome (APS). Methods. IgG and IgM an ti-beta(2)-GPI antibodies were determined by ELISA in 281 patients wit h SLE, primary APS, or other connective tissue diseases. Frequencies, sensitivities, specificities, and predictive values and correlations o f anti-beta(2)-GPI were compared to the aPL ELISA (IgG and IgM) and LA C for individual (and combined) features of APS. Results. Among 139 pa tients with positive aPL ELISA and/or LAC tests, 57 (41%) had anti-bet a(2)-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, an ti-beta(2)-GPI occurred in 42% and tended to be more specific but less sensitive than the aPL ELISA or LAG. When all 3 aPL tests were combin ed, the best sensitivities and negative predictive values were achieve d; however, specificity and positive predictive values remained low. A nti-beta(2)-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 LAG, 9 (11 %) were positive for anti-beta(2)-GPI, 7 of whom had clinical features consistent with APS (representing 5% of all with APS). Stepwise multi ple logistic regression analysis revealed beta(2)-GPI to be most stron gly associated with neurological syndromes other than stroke, deep ven ous thrombosis, and recurrent fetal loss, while LAC was most strongly correlated with stroke and thrombocytopenia. IgM aPL antibodies also w ere independently associated with neurological syndromes and recurrent fetal loss. Conclusion. Testing for beta(2)-GPI antibodies may be cli nically useful in the diagnosis of APS but cannot supplant other aPL E LISA or LAG. Multivariate analyses suggest that anti-beta-GPI antibodi es may play a more central role in certain clinical manifestations of APS than antibodies detected by the aPL ELISA or LAG.