Agalactosyl glycoforms of IgG autoantibodies are pathogenic.
The glycosylation of IgG results in many different glycoforms. A large body of correlative data (including remission of arthritis during pregnancy) has suggested that IgG molecules lacking galactose were associated with rheumatoid arthritis. We now demonstrate that agalactosyl IgG glycoforms are directly associated with pathogenicity in murine collagen-induced arthritis. We show that passive transfer of an acute synovitis in T-cell-primed mice can be enhanced by using IgG containing autoantibodies to type II collagen when the antibodies are present as the agalactosyl glycoform. Thus, nonpathogenic doses of autoantibodies can be made pathogenic by altering their glycosylation state.
Department of Biochemistry, University of Oxford, England.
T W
TW
Rademacher
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P
Williams
R A
RA
Dwek
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000503:physiopathology; D001323:Autoantibodies / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002645:Chickens; D003094:Collagen / Q000276:immunology; D005690:Galactose / Q000032:analysis*; D006031:Glycosylation; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000737:chemistry* / Q000276:immunology; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA / Q000276:immunology; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D001323:Autoantibodies; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D003094:Collagen; D005690:Galactose