Endoglycosidase treatment abrogates IgG arthritogenicity: importance of IgG glycosylation in arthritis.
The glycosylation status of IgG has been implicated in the pathology of rheumatoid arthritis. Earlier, we reported the identification of a novel secreted endo-beta-N-acetylglucosaminidase (EndoS), secreted by Streptococcus pyogenes that specifically hydrolyzes the beta-1,4-di-N-acetylchitobiose core of the asparagine-linked glycan of human IgG. Here, we analyzed the arthritogenicity of EndoS-treated collagen type II (CII)-specific mouse mAb in vivo. Endoglycosidase treatment of the antibodies inhibited the induction of arthritis in (BALB/c x B10.Q) F1 mice and induced a milder arthritis in B10.RIII mice as compared with the severe arthritis induced by non-treated antibodies. Furthermore, EndoS treatment did not affect the binding of IgG to CII and their ability to activate complement, but it resulted in reduced IgG binding to FcgammaR and disturbed the formation of stable immune complexes. Hence, the asparagine-linked glycan on IgG plays a crucial role in the development of arthritis.
Nandakumar
Kutty Selva
KS
Medical Inflammation Research, Lund University, Lund, Sweden. nan@med.lu.se
Collin
Mattias
M
Olsén
Arne
A
Nimmerjahn
Falk
F
Blom
Anna M
AM
Ravetch
Jeffrey V
JV
Holmdahl
Rikard
R
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001169:Arthritis, Experimental / Q000201:enzymology* / Q000276:immunology* / Q000517:prevention & control; D001426:Bacterial Proteins / Q000627:therapeutic use*; D050260:Carbohydrate Metabolism / Q000502:physiology; D024043:Collagen Type II / Q000276:immunology; D006026:Glycoside Hydrolases / Q000627:therapeutic use*; D006031:Glycosylation; D007074:Immunoglobulin G / Q000378:metabolism* / Q000633:toxicity*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D051381:Rats; D012720:Severity of Illness Index; D013297:Streptococcus pyogenes / Q000201:enzymology
D000911:Antibodies, Monoclonal; D001426:Bacterial Proteins; D024043:Collagen Type II; D007074:Immunoglobulin G; D006026:Glycoside Hydrolases; C431325:NDOS protein, Streptococcus pyogenes