IgG subclass distribution of antibodies against β2-GP1 and cardiolipin in patients with systemic lupus erythematosus and primary antiphospholipid syndrome, and their clinical associations

Objectives. To determine the immunoglobulin G (IgG) subclass distribution of anticardiolipin (aCL) and anti-beta (2)-glycoprotein 1 (beta (2)-GP1) antibodies (a beta (2)-GP1), and to examine possible associations between the different a beta (2)-GP1 and aCL subclasses and the main clinical manifestations of the antiphospholipid syndrome (APS). Methods. We studied 130 patients with systemic lupus erythematosus and 35 patients with primary APS. We used enzyme-linked immunosorbent assays to measure IgG aCL and a beta (2)-GP1 and to determine the IgG subclass distribution of these two autoantibodies. Results. When the number of patients positive for each subclass was examined, IgG(3) and IgG(2) aCL were more frequent (63.5 and 54.1% of patients were positive for the two subclasses, respectively), while for a beta (2)-GP1 IgG(2) was the most prevalent subclass (81.8% of patients were positive). IgG(2) aCL was significantly associated with arterial thrombosis (P=0.023) and fetal loss (P=0.013), and IgG(3) aCL was significantly associated with arterial thrombosis (P=0.0003) and fetal loss (P=0.045). IgG(2) a beta (2)-GP1 was associated with venous thrombosis (P=0.012) and IgG(3) a beta (2)-GP1 was associated with venous thrombosis (P=0.036) and fetal loss (P=0.024). Conclusions. The IgG(2) predominance of a beta (2)-GP1 suggests that the antibody response against beta (2)-GP1 may be T-cell-independent. As IgG(2) and IgG(3) differ in their effector functions, their association with the same clinical manifestations (i.e. thrombosis and fetal loss) suggests that more than one mechanism may be involved in the pathogenesis of thrombosis and fetal loss in APS.