High potential to reverse the inhibition of myeloperoxidase by ceruloplasmin of anti-myeloperoxidase autoantibodies of IgG3 subclass

Abstract

Among the four subclasses, anti-neutrophil cytoplasmic antibodies (ANCAs) against myeloperoxidase (MPO) IgG, IgG3 subclass was associated with severe disease. This study aimed to investigate some aspects of the in vitro pathogenic potential of MPO-ANCA of IgG3 subclass. IgG from plasma of 10 consecutive patients with positive MPO-ANCA was divided into the IgG poor in IgG3 and the IgG rich in IgG3 with protein A. Then, the ability to influence the oxidation activity of MPO, the ability to induce respiratory burst of neutrophils, and the ability to reverse the binding between ceruloplasmin (CP) and MPO were compared between the two fractions. The avidity of the MPO-ANCA-positive IgG rich in IgG3 was higher than that of the MPO-ANCA-positive IgG poor in IgG3 in 7 out of 10 patients. At the same antigen-binding level, the level of respiratory burst of neutrophils induced by the MPO-ANCA-positive IgG rich in IgG3 was significantly higher than that induced by the MPO-ANCA-positive IgG poor in IgG3 (1429.70 ± 137.85 vs. 1321.70 ± 244.51, P = 0.049, expressed by the mean fluorescence intensity); the binding level between MPO and CP after adding the MPO-ANCA-positive IgG rich in IgG3 was significantly lower than after adding the MPO-ANCA-positive IgG poor in IgG3 (0.599 ± 0.214 vs. 0.777 ± 0.353, P = 0.010, expressed by A 405); there was no significant difference in the MPO activity between adding the MPO-ANCA-positive IgG poor in IgG3 and rich in IgG3 (P = 0.217). In conclusion, MPO-ANCA of IgG3 subclass might have stronger ability to reverse the inhibition of MPO by CP than other subclasses.

Keywords::

• Antineutrophil cytoplasmic antibodies
• myeloperoxidase
• IgG3
• subclass
• ceruloplasmin