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

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Abstract
Objectives. To determine the immunoglobulin G (IgG) subclass distribution of anticardiolipin (aCL) and anti‐β2‐glycoprotein 1 (β2‐GP1) antibodies (aβ2‐GP1), and to examine possible associations between the different aβ2‐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 aβ2‐GP1 and to determine the IgG subclass distribution of these two autoantibodies. Results. When the number of patients positive for each subclass was examined, IgG3 and IgG2 aCL were more frequent (63.5 and 54.1% of patients were positive for the two subclasses, respectively), while for aβ2‐GP1 IgG2 was the most prevalent subclass (81.8% of patients were positive). IgG2 aCL was significantly associated with arterial thrombosis (P=0.023) and fetal loss (P=0.013), and IgG3 aCL was significantly associated with arterial thrombosis (P=0.0003) and fetal loss (P=0.045). IgG2 aβ2‐GP1 was associated with venous thrombosis (P=0.012) and IgG3 aβ2‐GP1 was associated with venous thrombosis (P=0.036) and fetal loss (P=0.024). Conclusions. The IgG2 predominance of aβ2‐GP1 suggests that the antibody response against β2‐GP1 may be T‐cell‐independent. As IgG2 and IgG3 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.