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IgA subclasses have different effector functions associated with distinct glycosylation profiles

Author

Listed:
  • 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)

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.

Suggested Citation

  • 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 Hartma, 2020. "IgA subclasses have different effector functions associated with distinct glycosylation profiles," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-13992-8
    DOI: 10.1038/s41467-019-13992-8
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    Cited by:

    1. Anna Halama & Shaza Zaghlool & Gaurav Thareja & Sara Kader & Wadha Al Muftah & Marjonneke Mook-Kanamori & Hina Sarwath & Yasmin Ali Mohamoud & Nisha Stephan & Sabine Ameling & Maja Pucic Baković & Jan, 2024. "A roadmap to the molecular human linking multiomics with population traits and diabetes subtypes," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    2. Janice Z. Jia & Carolyn A. Cohen & Haogao Gu & Milla R. McLean & Raghavan Varadarajan & Nisha Bhandari & Malik Peiris & Gabriel M. Leung & Leo L. M. Poon & Tim Tsang & Amy W. Chung & Benjamin J. Cowli, 2024. "Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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