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  • Review Article
  • Published:

Differential antibody glycosylation in autoimmunity: sweet biomarker or modulator of disease activity?

Nature Reviews Rheumatology volume 13, pages 621–630 (2017)Cite this article

Subjects

Key Points

  • Serum and/or autoantibody glycosylation is altered in many autoantibody-dependent and autoantibody-independent autoimmune diseases

  • IgG glycosylation is a key regulator of (auto)antibody activity

  • IgG glycovariants lacking galactose and sialic acid residues can appear before the onset of disease symptoms

  • IgG sialylation impairs pro-inflammatory antibody activity and might also explain why autoantibodies can be present in patients with inactive, or no disease

  • A high level of IgG galactosylation and sialylation can confer active anti-inflammatory activity

  • Distinct sets of Fc receptors are involved in pro-inflammatory and anti-inflammatory antibody activity

Abstract

A loss of humoral tolerance is a hallmark of many autoimmune diseases and the detection of self-reactive antibodies (autoantibodies) of the immunoglobulin G (IgG) isotype is widely used as a biomarker and diagnostic tool. However, autoantibodies might also be present in individuals without autoimmune disease, thus limiting their usefulness as a sole indicator of disease development. Moreover, while clear evidence exists of the pathogenic effects of autoantibodies in mouse model systems, the contribution of autoantibodies to the pathology of many autoimmune diseases has yet to be established. In this Review, the authors discuss the changes in total serum IgG and autoantibody glycosylation that occur during autoimmune disease and how these changes might help to predict disease development in the future. Furthermore, current knowledge of the signals regulating antibody glycosylation and how individual antibody glycoforms could be used to optimize current treatment approaches will be discussed.

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Figure 1: Effects of IgG glycosylation on antigen recognition and effector functions.
Figure 2: Influence of fucosylation on IgG effector functions.
Figure 3: Effect of sialylated glycoforms on IgG activity.

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Acknowledgements

We would like to apologize to all our colleagues whose important work could not be cited directly due to constraints of space. These references can be found in the review articles cited in this manuscript. This work was funded through a grant from the German Research Foundation (CRC1181-TP A7). Images displayed in Fig. 2A were kindly provided by Peter Sondermann.

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  1. Department of Biology, Institute of Genetics, University of Erlangen-Nuremberg, Erwin-Rommel-Str. 3, Erlangen, 91058, Germany

    Michaela Seeling, Christin Brückner & Falk Nimmerjahn

  2. Department of Biology, Medical Immunology Campus Erlangen, University of Erlangen-Nuremberg, Staudtstr. 5, Erlangen, 91058, Germany

    Falk Nimmerjahn

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  1. Michaela Seeling
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F.N. made a substantial contribution to discussion of the content. All authors wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Falk Nimmerjahn.

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Seeling, M., Brückner, C. & Nimmerjahn, F. Differential antibody glycosylation in autoimmunity: sweet biomarker or modulator of disease activity?. Nat Rev Rheumatol 13, 621–630 (2017). https://doi.org/10.1038/nrrheum.2017.146

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