Glycosylation of IgG, immune complexes and IgG subclasses in the MRL-lpr/lpr mouse model of rheumatoid arthritis.
The MRL-lpr/lpr (MRL/lpr) mouse spontaneously develops a disease syndrome which, in many respects, is similar to human rheumatoid arthritis. These mice developed joint inflammation, circulating rheumatoid factors and immune complexes. We now show that the parallel with human disease extends to a glycosylation defect which is observed on IgG from rheumatoid arthritis patients. Using the lectins ricin and Bandeiraea simplicifolia II we have found that terminal N-acetylglucosamine is clearly raised in MRL/lpr IgG. Increased exposure of galactose was also detected, indicating that a second glycosylation site must be present on these molecules. Polyethylene glycol-precipitated IgG complexes bound significantly more of each lectin than did free IgG, indicating that the changes in glycosylation were associated with complex formation. The sugar abnormality was most marked in the IgG2a/IgG3 fraction from protein A IgG subclass chromatography. Our results suggest that the IgG glycosylation defect seen in rheumatoid arthritis is apparent in the MRL/lpr mouse and may contribute, through complex formation, to the pathological processes in the rheumatoid syndrome.
Bond
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Division of Immunology, St. George's Hospital Medical School, London.
Cooke
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Hay
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D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D000936:Antigen-Antibody Complex / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D002240:Carbohydrate Sequence; D004195:Disease Models, Animal; D005690:Galactose / Q000378:metabolism; D006031:Glycosylation; D007074:Immunoglobulin G / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism; D011499:Protein Processing, Post-Translational
D000936:Antigen-Antibody Complex; D007074:Immunoglobulin G; D037102:Lectins; D009844:Oligosaccharides; D000117:Acetylglucosamine; D005690:Galactose