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

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Clin Immunol. 2023 Nov 2:109817. doi: 10.1016/j.clim.2023.109817. Online ahead of print.

ABSTRACT

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.

PMID:37925120 | DOI:10.1016/j.clim.2023.109817


Source: https://pubmed.ncbi.nlm.nih.gov/3792512 ... t6+86293ac