IgG subclass distribution, affinity of anti-myeloperoxidase antibodies in sera from patients with Wegener's granulomatosis and microscopic polyangiitis

Abstract

Aim: Our previous study suggested that patients with MPO-ANCA (myeloperoxidase antineutrophil cytoplasmic autoantibodies)-positive Wegener's granulomatosis (WG) were common in Chinese, indicating that patients with MPO-ANCA could manifest as either WG or microscopic polyangiitis (MPA). The aim of this study was to compare the immunological characteristics of MPO-ANCA in patients with WG and MPA.

Methods: Fifteen patients with WG and 21 patients with MPA were enrolled in the current study. Anti-MPO IgG subclasses and their titres were detected by antigen-specific enzyme-linked immunosorbent assays (ELISA); affinity was assessed by antigen-inhibition ELISAs. The sera from all patients were employed to inhibit biotin conjugated affinity-purified human anti-MPO antibodies (Probe-biotin), from plasma exchange of a patient with MPA, in a competitive inhibition ELISAs system.

Results: All four anti-MPO subclasses could be detected in sera from patients with WG and MPA. The titres of anti-MPO IgG4 subclass in patients with WG were significantly higher than those with MPA (1:1878 vs 1:218, P < 0.005). The affinity constants of MPO-ANCA were comparable between patients with WG and MPA (0.3-70/M vs 0.3-140/M respectively). Eleven out of the 15 sera and 18 out of the 21 sera could inhibit the binding of the Probe-biotin in patients with WG and MPA respectively. The average inhibition rate was 47.7% +/- 11.5% and 61.7% +/- 14.5% respectively (P < 0.05).

Conclusion: MPO-ANCA IgG4 subclass might play a role in the development of WG. The MPO-ANCA in WG and MPA might recognize overlapping but different epitopes on native MPO molecule. The difference in immunological characteristics of MPO-ANCA might contribute to different disease entities.