IgA subclasses have different effector functions associated with distinct glycosylation profiles

Steffen U, Koeleman CA, Sokolova MV, Bang H, Kleyer A, Rech J, Unterweger H, Schicht M, Garreis F, Hahn J, Andes FT, Hahn M, Mahajan A, Paulsen F, Hoffmann M, Lochnit G, Munoz LE, Wuhrer M, Falck D, Herrmann M, Schett G, Hartmann F (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Nature Communications Nature Publishing Group: Nature Communications

Book Volume: 11

Article Number: 120

Journal Issue: 1

DOI: 10.1038/s41467-019-13992-8

Abstract

Monomeric serum immunoglobulin A (IgA) can contribute to the development of various autoimmune diseases, but the regulation of serum IgA effector functions is not well defined. Here, we show that the two IgA subclasses (IgA1 and IgA2) differ in their effect on immune cells due to distinct binding and signaling properties. Whereas IgA2 acts pro-inflammatory on neutrophils and macrophages, IgA1 does not have pronounced effects. Moreover, IgA1 and IgA2 have different glycosylation profiles, with IgA1 possessing more sialic acid than IgA2. Removal of sialic acid increases the pro-inflammatory capacity of IgA1, making it comparable to IgA2. Of note, disease-specific autoantibodies in patients with rheumatoid arthritis display a shift toward the pro-inflammatory IgA2 subclass, which is associated with higher disease activity. Taken together, these data demonstrate that IgA effector functions depend on subclass and glycosylation, and that disturbances in subclass balance are associated with autoimmune disease.

Authors with CRIS profile

Ulrike Steffen Department of Medicine 3 – Rheumatology and Immunology Arnd Kleyer Department of Medicine 3 – Rheumatology and Immunology Hans Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology Harald Unterweger Department of Otorhinolaryngology – Head and Neck Surgery Martin Schicht Lehrstuhl für Funktionelle und Klinische Anatomie Fabian Garreis Lehrstuhl für Funktionelle und Klinische Anatomie Jonas Hahn Department of Medicine 3 – Rheumatology and Immunology Aparna Mahajan Department of Medicine 3 – Rheumatology and Immunology Friedrich Paulsen Lehrstuhl für Funktionelle und Klinische Anatomie Markus Hoffmann Department of Medicine 3 – Rheumatology and Immunology Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III

Involved external institutions

ORGENTEC Diagnostika GmbH DE Germany (DE) Leiden University Medical Center NL Netherlands (NL) Justus-Liebig-Universität Gießen DE Germany (DE)

How to cite

APA:

Steffen, U., Koeleman, C.A., Sokolova, M.V., Bang, H., Kleyer, A., Rech, J.,... Hartmann, F. (2020). IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nature Communications, 11(1). https://doi.org/10.1038/s41467-019-13992-8

MLA:

Steffen, Ulrike, et al. "IgA subclasses have different effector functions associated with distinct glycosylation profiles." Nature Communications 11.1 (2020).

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