IgG subclass distribution of antibodies against beta(2)-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 o f anticardiolipin (aCL) and anti-beta (2)-glycoprotein 1 (beta (2)-GP1) ant ibodies (a beta (2)-GP1), and to examine possible associations between the different a beta (2)-GP1 and aCL subclasses and the main clinical manifesta tions of the antiphospholipid syndrome (APS). Methods. We studied 130 patients with systemic lupus erythematosus and 35 p atients with primary APS. We used enzyme-linked immunosorbent assays to mea sure IgG aCL and a beta (2)-GP1 and to determine the IgG subclass distribut ion of these two autoantibodies. Results. When the number of patients positive for each subclass was examine d, IgG(3) and IgG(2) aCL were more frequent (63.5 and 54.1% of patients wer e 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). I gG(2) aCL was significantly associated with arterial thrombosis (P=0.023) a nd fetal loss (P=0.013), and IgG(3) aCL was significantly associated with a rterial thrombosis (P=0.0003) and fetal loss (P=0.045). IgG(2) a beta (2)-G P1 was associated with venous thrombosis (P=0.012) and IgG(3) a beta (2)-GP 1 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 an tibody response against beta (2)-GP1 may be T-cell-independent. As IgG(2) a nd IgG(3) differ in their effector functions, their association with the sa me clinical manifestations (i.e. thrombosis and fetal loss) suggests that m ore than one mechanism may be involved in the pathogenesis of thrombosis an d fetal loss in APS.