Autoantibody activity of IgG rheumatoid factor increases with decreasing levels of galactosylation and sialylation.
The occurrence of N-linked oligosaccharides lacking galactose is significantly higher than normal in serum IgG of patients with rheumatoid arthritis (RA) in whom rheumatoid factor (RF), an autoantibody against autologous IgG, has been detected. In the present study, IgGs with and without RF activity (IgGRF and non-RF IgG, respectively) were prepared from sera of RA patients, and their oligosaccharide structures were characterized in order to investigate the relationship between RF activity and glycosylation. Three IgGRF fractions and a non-RF IgG fraction were obtained based on their ability to bind to an IgG-Sepharose column. The specific RF activity, as measured by immunoassays, was highest in the IgGRF fraction, which bound most avidly to the IgG-Sepharose. When the oligosaccharides were released by hydrazinolysis, and analyzed by MALDI-TOF mass spectrometry and HPLC, in combination with sequential exoglycosidase treatment, all the IgG samples were found to contain a series of biantennary complex-type oligosaccharides. The incidence of galactose-free oligosaccharides was significantly higher in both IgGRFs and non-RF IgG from RA patients compared with IgG from healthy individuals. In all IgGRFs, the levels of sialylation and galactosylation were lower than those in non-RF IgG from RA patients; the sialylation of non-RF IgG was the same as that of IgG from healthy individuals. In addition, the decreases in galactosylation and sialylation of oligosaccharides in IgGRF correlated well with the increase in RF activity. These findings could contribute to our understanding of the mechanisms of IgG-IgG complex formation and the pathogenicity of these complexes in RA patients.
Matsumoto
A
A
Department of Applied Biochemistry, Tokai University, Hiratsuka, Kanagawa 259-1292, Japan.
Shikata
K
K
Takeuchi
F
F
Kojima
N
N
Mizuochi
T
T
D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005690:Galactose / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism; D016555:Matched-Pair Analysis; D008875:Middle Aged; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009844:Oligosaccharides / Q000032:analysis / Q000737:chemistry; D012217:Rheumatoid Factor / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000378:metabolism*
D007074:Immunoglobulin G; D009844:Oligosaccharides; D012217:Rheumatoid Factor; D019158:N-Acetylneuraminic Acid; D005690:Galactose