Abstract
A unique anti-inflammatory property of IgG, independent of antigen specificity, is described. IgG with modification of the heavy-chain glycan on asparagine 297 by the streptococcal enzyme endo-β-N-acetylglucosaminidase (EndoS) induced a dominant suppression of immune complex (IC)-mediated inflammation, such as arthritis, through destabilization of local ICs by fragment crystallizable-fragment crystallizable (Fc-Fc) interactions. Small amounts (250 µg) of EndoS-hydrolyzed IgG were sufficient to inhibit arthritis in mice and most effective during the formation of ICs in the target tissue. The presence of EndoS-hydrolyzed IgG disrupted larger IC lattice formation both in vitro and in vivo, as visualized with anti-C3b staining. Neither complement binding in vitro nor antigen-antibody binding per se was affected.
Keywords:
collagen; endoglycosidase; glycosylation; monoclonal antibody; rheumatoid arthritis.
Publication types
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Research Support, Non-U.S. Gov't
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Retracted Publication
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / metabolism
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Antibodies, Monoclonal / pharmacology
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Antigen-Antibody Complex / immunology*
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Arthritis, Experimental / immunology*
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Arthritis, Experimental / therapy*
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Arthritis, Rheumatoid / immunology
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Arthritis, Rheumatoid / therapy
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Cartilage / immunology
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Cattle
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Complement C3b / immunology
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Complement C3b / metabolism
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Disease Models, Animal
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Glycoside Hydrolases / immunology
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Glycoside Hydrolases / metabolism
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Glycosylation
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Immune Tolerance / immunology*
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Immunoglobulin G / immunology*
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Immunoglobulin G / metabolism
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Immunoglobulin G / pharmacology
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Inflammation / immunology
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Inflammation / therapy
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Mice
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Polysaccharides / immunology
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Rats
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Receptors, IgG / immunology
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Receptors, IgG / metabolism
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Streptococcus pyogenes / enzymology
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Tissue Culture Techniques
Substances
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Antibodies, Monoclonal
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Antigen-Antibody Complex
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Immunoglobulin G
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Polysaccharides
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Receptors, IgG
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glycosylated IgG
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Complement C3b
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Glycoside Hydrolases