In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner.

Albert H, Collin M, Dudziak D, Ravetch JV, Nimmerjahn F (2008)

Publication Status: Published

Publication Type: Journal article

Publication year: 2008

Journal

Proceedings of the National Academy of Sciences of the United States of America National Academy of Sciences

Book Volume: 105

Pages Range: 15005-9

Journal Issue: 39

DOI: 10.1073/pnas.0808248105

Abstract

IgG antibodies are potent inducers of proinflammatory responses. During autoimmune diseases such as arthritis and systemic lupus erythematosus, IgG autoantibodies are responsible for the chronic inflammation and destruction of healthy tissues by cross-linking Fc receptors on innate immune effector cells. The sugar moiety attached to the asparagine-297 residue in the constant domain of the antibody is critical for the overall structure and function of the molecule. Removal of this sugar domain leads to the loss of the proinflammatory activity, suggesting that in vivo modulation of antibody glycosylation might be a strategy to interfere with autoimmune processes. In this work, we investigated whether removal of the majority of the IgG-associated sugar domain by endoglycosidase S (EndoS) from Streptococcus pyogenes is able to interfere with autoimmune inflammation. We demonstrate that EndoS injection efficiently removes the IgG-associated sugar domain in vivo and interferes with autoantibody-mediated proinflammatory processes in a variety of autoimmune models. Importantly, however, we observed a differential impact of EndoS-mediated sugar side chain hydrolysis on IgG activity depending on the individual IgG subclass.

Authors with CRIS profile

Heike Albert Lehrstuhl für Genetik Diana Dudziak Professur für die Biologie Dendritischer Zellen Falk Nimmerjahn Lehrstuhl für Genetik

Involved external institutions

Lund University / Lunds universitet SE Sweden (SE) Rockefeller University US United States (USA) (US)

How to cite

APA:

Albert, H., Collin, M., Dudziak, D., Ravetch, J.V., & Nimmerjahn, F. (2008). In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner. Proceedings of the National Academy of Sciences of the United States of America, 105(39), 15005-9. https://doi.org/10.1073/pnas.0808248105

MLA:

Albert, Heike, et al. "In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner." Proceedings of the National Academy of Sciences of the United States of America 105.39 (2008): 15005-9.

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