In vivo enzymatic modulation of IgG glycosylation inhibits autoimmune disease in an IgG subclass-dependent manner.
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.
Albert
Heike
H
Laboratory of Experimental Immunology and Immunotherapy, Medical Department 3, Nikolaus-Fiebiger-Centre, University of Erlangen-Nuremberg, Glueckstrasse 6, 91054 Erlangen, Germany.
Collin
Mattias
M
Dudziak
Diana
D
Ravetch
Jeffrey V
JV
Nimmerjahn
Falk
F
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage*; D006026:Glycoside Hydrolases / Q000008:administration & dosage*; D006031:Glycosylation; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000097:blood / Q000187:drug effects* / Q000276:immunology; D007269:Injections, Intra-Arterial; D051379:Mice; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000378:metabolism
D001323:Autoantibodies; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D011134:Polysaccharides; D006026:Glycoside Hydrolases; C431325:NDOS protein, Streptococcus pyogenes