IgA subclasses have different effector functions associated with distinct glycosylation profiles

Ulrike Steffen (), Carolien A. Koeleman, Maria V. Sokolova, Holger Bang, Arnd Kleyer, Jürgen Rech, Harald Unterweger, Martin Schicht, Fabian Garreis, Jonas Hahn, Fabian T. Andes, Fabian Hartmann, Madelaine Hahn, Aparna Mahajan, Friedrich Paulsen, Markus Hoffmann, Günter Lochnit, Luis E. Muñoz, Manfred Wuhrer, David Falck, Martin Herrmann and Georg Schett ()
Additional contact information
Ulrike Steffen: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Carolien A. Koeleman: Leiden University Medical Center, Center for Proteomics and Metabolomics, Glycomics and Clinical Proteomics Group
Maria V. Sokolova: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Holger Bang: Orgentec Diagnostika
Arnd Kleyer: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Jürgen Rech: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Harald Unterweger: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Martin Schicht: Friedrich Alexander University Erlangen-Nürnberg
Fabian Garreis: Friedrich Alexander University Erlangen-Nürnberg
Jonas Hahn: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Fabian T. Andes: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Fabian Hartmann: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Madelaine Hahn: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Aparna Mahajan: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Friedrich Paulsen: Friedrich Alexander University Erlangen-Nürnberg
Markus Hoffmann: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Günter Lochnit: Justus-Liebig-University Giessen
Luis E. Muñoz: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Manfred Wuhrer: Leiden University Medical Center, Center for Proteomics and Metabolomics, Glycomics and Clinical Proteomics Group
David Falck: Leiden University Medical Center, Center for Proteomics and Metabolomics, Glycomics and Clinical Proteomics Group
Martin Herrmann: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen
Georg Schett: Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41467-019-13992-8

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