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

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.