IgA subclasses have different effector functions associated with distinct glycosylation profiles

Nature Communications, vol. 11, pp. 120

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 22

1. Ulrike Steffen corresponding

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany. ulrike.steffen@uk-erlangen.de

   Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

2. Carolien A. M. Koeleman Aachen Center for Proteomics and Metabolomics Glycomics and Clinical Proteomics Group

   Leiden University Medical Center

   Affiliation as printed

   Leiden University Medical Center, Center for Proteomics and Metabolomics, Glycomics and Clinical Proteomics Group, Leiden, Netherlands

3. Maria V Sokolova

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

   Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

4. Holger Bang
   Affiliation as printed

   Orgentec Diagnostika, Mainz, Germany

5. Arnd Kleyer

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

   Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

6. Jürgen Rech

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

   Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

7. Harald Unterweger

   Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

   Affiliation as printed

   Section of Experimental Oncology and Nanomedicine (SEON), ENT Department, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

8. Martin Schicht

   Friedrich-Alexander-Universität Erlangen-Nürnberg

   Affiliation as printed

   Institute of Functional and Clinical Anatomy, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

9. Fabian Garreis

   Friedrich-Alexander-Universität Erlangen-Nürnberg

   Affiliation as printed

   Institute of Functional and Clinical Anatomy, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

10. Jonas Hahn

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

11. Fabian T. Andes

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

12. F Hartmann

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

13. Madelaine Hahn

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

14. Aparna Mahajan

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

15. Friedrich P. Paulsen

    Friedrich-Alexander-Universität Erlangen-Nürnberg

    Affiliation as printed

    Institute of Functional and Clinical Anatomy, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany

16. Markus H. Hoffmann

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

17. Günter Lochnit

    Justus-Liebig-Universität Gießen

    Affiliation as printed

    Protein Analytics, Institute of Biochemistry, Faculty of Medicine, Justus-Liebig-University Giessen, Giessen, Germany

18. Luis Enrique Munoz

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

19. Manfred Wuhrer Aachen Center for Proteomics and Metabolomics Glycomics and Clinical Proteomics Group

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center, Center for Proteomics and Metabolomics, Glycomics and Clinical Proteomics Group, Leiden, Netherlands

20. David Falck Aachen Center for Proteomics and Metabolomics Glycomics and Clinical Proteomics Group

    Leiden University Medical Center

    Affiliation as printed

    Leiden University Medical Center, Center for Proteomics and Metabolomics, Glycomics and Clinical Proteomics Group, Leiden, Netherlands

21. Martin Herrmann i

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany

22. Georg Andreas Schett corresponding

    Friedrich-Alexander-Universität Erlangen-Nürnberg · Universitätsklinikum Erlangen

    Affiliation as printed

    Department of Internal Medicine 3-Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany. georg.schett@uk-erlangen.de

    Department of Internal Medicine 3—Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany