TY - JOUR
T1 - Autoantibody subclass predominance is not driven by aberrant class switching or impaired B cell development
AU - Paardekooper, Laurent M.
AU - Fillié-Grijpma, Yvonne E.
AU - van der Sluijs-Gelling, Alita J.
AU - Zlei, Mihaela
AU - van Doorn, Remco
AU - Vermeer, Maarten H.
AU - Paunovic, Manuela
AU - Titulaer, Maarten J.
AU - van der Maarel, Silvère M.
AU - van Dongen, Jacques J.M.
AU - Verschuuren, Jan J.
AU - Huijbers, Maartje G.
AU - T2B Consortium
N1 - Publisher Copyright:
© 2023 The Authors
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85180003623&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2023.109817
DO - 10.1016/j.clim.2023.109817
M3 - Article
C2 - 37925120
AN - SCOPUS:85180003623
SN - 1521-6616
VL - 257
JO - Clinical Immunology
JF - Clinical Immunology
M1 - 109817
ER -