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

Clinical Immunology, vol. 257, pp. 109817

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.

Authors 12

1. Laurent M. Paardekooper Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

2. Yvonne E. Fillié‐Grijpma Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

3. Alita J. van der Sluijs‐Gelling Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands

4. Mihaela Zlei Aachen Department of Immunology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands

5. Remco van Doorn Aachen Department of Dermatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

6. Maarten H. Vermeer Aachen Department of Dermatology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands

7. Manuela Paunovic

   Erasmus MC

   Affiliation as printed

   Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands

8. Maarten J. Titulaer

   Erasmus MC

   Affiliation as printed

   Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands

9. Silvère M. van der Maarel Aachen Department of Human Genetics

   Leiden University Medical Center

   Affiliation as printed

   Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

10. Jacques J. M. van Dongen Aachen Department of Immunology, Leiden University Medical Center

    Consejo Superior de Investigaciones Científicas · Universidad de Salamanca · Leiden University Medical Center · Centro de Investigación del Cáncer · Instituto de Biología Molecular y Celular del Cáncer de Salamanca

    Affiliation as printed

    Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands; Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC, USAL-CSIC-FICUS) and Department of Medicine, University of Salamanca, Salamanca, Spain

    Centro de Investigación del Cáncer-Instituto de Biología Molecular y Celular del Cáncer (CIC-IBMCC, USAL-CSIC-FICUS) and Department of Medicine, University of Salamanca, Salamanca, Spain

    Department of Immunology, Leiden University Medical Center, Leiden, The Netherlands

11. Jan J.G.M. Verschuuren Aachen Department of Neurology, Leiden University Medical Center (LUMC)

    Leiden University Medical Center

    Affiliation as printed

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands

12. Maartje G. M. Huijbers corresponding Aachen Department of Human Genetics Department of Neurology, Leiden University Medical Center (LUMC)

    Leiden University Medical Center

    Affiliation as printed

    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands; Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: m.g.m.huijbers@lumc.nl

    Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

    Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands