title: Dominant suppression of inflammation by glycan-hydrolyzed IgG.
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.
authors.affiliation: Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institute, 171 77 Stockholm, Sweden. Nandakumar.Kutty-Selva@ki.se
authors.forename: Kutty Selva
authors.initials: KS
authors.lastname: Nandakumar
authors.forename: Mattias
authors.initials: M
authors.lastname: Collin
authors.forename: Kaisa E
authors.initials: KE
authors.lastname: Happonen
authors.forename: Allyson M
authors.initials: AM
authors.lastname: Croxford
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Lundström
authors.forename: Roman A
authors.initials: RA
authors.lastname: Zubarev
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Rowley
authors.forename: Anna M
authors.initials: AM
authors.lastname: Blom
authors.forename: Rikard
authors.initials: R
authors.lastname: Holmdahl
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology* / Q000628:therapy*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy; D002356:Cartilage / Q000276:immunology; D002417:Cattle; D003179:Complement C3b / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006026:Glycoside Hydrolases / Q000276:immunology / Q000378:metabolism; D006031:Glycosylation; D007108:Immune Tolerance / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D051379:Mice; D011134:Polysaccharides / Q000276:immunology; D051381:Rats; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D013297:Streptococcus pyogenes / Q000201:enzymology; D046509:Tissue Culture Techniques; D006023:Glycoproteins
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D003179:Complement C3b; D006026:Glycoside Hydrolases; D007074:Immunoglobulin G; D011134:Polysaccharides; D017452:Receptors, IgG; C046179:glycosylated IgG; D006023:Glycoproteins
keywords: collagen; endoglycosidase; glycosylation; monoclonal antibody; rheumatoid arthritis