Comprehensive overview of autoantibody isotype and subclass distribution

Mikhail Volkov*, Mariateresa Coppola, T2B Consortium, Ruth Huizinga, Filip Eftimov, Tom W.J. Huizinga, Anneke J. van der Kooi, Liesbeth E.M. Oosten, Joost Raaphorst, Theo Rispens, Rocco Sciarrillo, Maarten J. Titulaer, Luuk Wieske, René E.M. Toes, Maartje G.M. Huijbers, Karin A. van Schie, Diane van der Woude

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

15 Citations (Scopus)
72 Downloads (Pure)

Abstract

The presence of autoreactive antibodies is a hallmark of many autoimmune diseases. The effector functions of (auto)antibodies are determined by their constant domain, which defines the antibody isotype and subclass. The most prevalent isotype in serum is IgG, which is often the only isotype used in diagnostic testing. Nevertheless, autoantibody responses can have their own unique isotype/subclass profile. Because comparing autoantibody isotype profiles may yield new insights into disease pathophysiology, here we summarize the isotype/subclass profiles of the most prominent autoantibodies. Despite substantial variation between (and within) autoantibody responses, this unprecedented comparison shows that autoantibodies share distinctive isotype patterns across different diseases. Although most autoantibody responses are dominated by IgG (and mainly IgG1), several specific diseases are characterized by a predominance of IgG4. In other diseases, IgE plays a key role. Importantly, shared features of autoantibody isotype/subclass profiles are seen in clinically unrelated diseases, suggesting potentially common trajectories in response evolution, disease pathogenesis, and treatment response. Isotypes beyond IgG are scarcely investigated in many autoantibody responses, leaving substantial gaps in our understanding of the pathophysiology of autoimmune diseases. Future research should address isotype/subclass profiling in more detail and incorporate autoantibody measurements beyond total IgG in disease models and clinical studies.

Original languageEnglish
Pages (from-to)999-1010
Number of pages12
JournalJournal of Allergy and Clinical Immunology
Volume150
Issue number5
DOIs
Publication statusPublished - 1 Nov 2022

Bibliographical note

Funding Information:
This work was supported by the PPP Allowance made available by Top Sector Life Sciences & Health to Samenwerkende Gezondheidsfondsen (SGF) under project number LSHM18055-SGF to stimulate public-private partnerships and cofinancing by health foundations that are part of the SGF.

Publisher Copyright: © 2022 The Authors

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