Antibodies to age‐β2glycoprotein I in patients with anti‐phospholipid antibody syndrome

Abstract

Anti‐phospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized clinically by arterial and/or venous thromboses, recurrent abortions or fetal loss and serologically by the presence of ‘anti‐phospholipid antibodies’ (aPL). The main target antigen of the antibodies is β2glycoprotein I (β2GPI). Post‐translational oxidative modifications of the protein have been widely described. In this study we aimed to analyse sera reactivity to glucose‐modified β2GPI (G‐β2GPI). Sera collected from 43 patients with APS [15 primary APS (PAPS) and 28 APS associated with systemic lupus erythematosus (SLE) (SAPS)], 30 with SLE, 30 with rheumatoid arthritis (RA) and 40 healthy subjects were analysed by an enzyme‐linked immunosorbent assay (ELISA) using a G‐β2GPI. Nine of 15 consecutive PAPS out‐patients (60%) and 16 of 28 SAPS (57.1%) showed serum antibodies [immunoglobulin (Ig)G class] against G‐β2GPI (anti‐G‐β2GPI) by ELISA. The occurrence of anti‐G‐β2GPI was significantly higher in APS patients compared to patients suffering from SLE. No RA patients or control healthy subjects resulted positive for anti‐G‐β2GPI. Of note, aG‐β2GPI prompted to identify some APS patients (four PAPS and seven SAPS), who were negative in the classical anti‐β2GPI test. Moreover, in APS patients, anti‐G‐β2GPI titre was associated significantly with venous thrombosis and seizure in APS patients. This study demonstrates that G‐β2GPI is a target antigen of humoral immune response in patients with APS, suggesting that β2GPI glycation products may contain additional epitopes for anti‐β2GPI reactivity. Searching for these antibodies may be useful for evaluating the risk of clinical manifestations.