Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development

Paardekooper, L.M.; Fillié-Grijpma, Y.E.; Sluijs-gelling, A.J. van der; Zlei, M.; Doorn, R. van; Vermeer, M.H.; ... ; T2B Consortium (2023)

Article / Letter to editor

A subset of autoimmune diseases is characterized by predominant pathogenic IgG4 autoantibodies (IgG4-AID). Why IgG4 predominates in these disorders is unknown. We hypothesized that dysregulated B cell maturation or aberrant class switching causes overrepresentation of IgG4⁺ B cells and plasma cells. Therefore, we compared the B cell compartment of patients from four different IgG4-AID with two IgG1-3-AID and healthy donors, using flow cytometry. Relative subset abundance at all maturation stages was normal, except for a, possibly treatment-related, reduction in immature and naïve CD5⁺ cells. IgG4⁺ B cell and plasma cell numbers were normal in IgG4-AID patients, however they had a (sub)class-independent 8-fold increase in circulating CD20^-CD138⁺ cells. No autoreactivity was found in this subset. These results argue against aberrant B cell development and rather suggest the autoantibody subclass predominance to be antigen-driven. The similarities between IgG4-AID suggest that, despite displaying variable clinical phenotypes, they share a similar underlying immune profile.

• IgG4
• Myasthenia gravis
• Pemphigus
• Autoimmune encephalitis
• Plasma cells

• All authors: Paardekooper, L.M.; Fillié-Grijpma, Y.E.; Sluijs-gelling, A.J. van der; Zlei, M.; Doorn, R. van; Vermeer, M.H.; Paunovic, M.; Titulaer, M.J.; Maarel, S.M. van der; Dongen, J.J.M. van; Verschuuren, J.J.; Huijbers, M.G.; T2B Consortium
• Date: 2023-11-16
• Journal: Clinical Immunology
• Volume: 257
• DOI: doi:10.1016/j.clim.2023.109817
• Link: https://www.sciencedirect.com/science/article/pii/S1521661623005806?via%...