Antibodies to age‐β 2 glycoprotein I in patients with anti‐phospholipid antibody syndrome

Summary 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 β 2 glycoprotein I (β 2 GPI). Post‐translational oxidative modifications of the protein have been widely described. In this study we aimed to analyse sera reactivity to glucose‐modified β 2 GPI (G‐β 2 GPI). 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‐β 2 GPI. Nine of 15 consecutive PAPS out‐patients (60%) and 16 of 28 SAPS (57.1%) showed serum antibodies [immunoglobulin (Ig)G class] against G‐β 2 GPI (anti‐G‐β 2 GPI) by ELISA. The occurrence of anti‐G‐β 2 GPI was significantly higher in APS patients compared to patients suffering from SLE. No RA patients or control healthy subjects resulted positive for anti‐G‐β 2 GPI. Of note, aG‐β 2 GPI prompted to identify some APS patients (four PAPS and seven SAPS), who were negative in the classical anti‐β 2 GPI test. Moreover, in APS patients, anti‐G‐β 2 GPI titre was associated significantly with venous thrombosis and seizure in APS patients. This study demonstrates that G‐β 2 GPI is a target antigen of humoral immune response in patients with APS, suggesting that β 2 GPI glycation products may contain additional epitopes for anti‐β 2 GPI reactivity. Searching for these antibodies may be useful for evaluating the risk of clinical manifestations.