Autoantibody activity of IgG rheumatoid factor increases with decreasing levels of galactosylation and sialylation

The occurrence of N-linked oligosaccharides lacking galactose is significan tly 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 patient s, and their oligosaccharide structures were characterized in order to inve stigate the relationship between RF activity and glycosylation, Three IgGRF fractions and a non-RF IgG fraction were obtained based on their ability t o bind to an IgG-Sepharose column, The specific RF activity, as measured by immunoassays, was highest in the IgGRF fraction, which bound most avidly t o the IgG-Sepharose, When the oligosaccharides were released by hydrazinoly sis, and analyzed by MALDI-TOF mass spectrometry and HPLC, in combination w ith sequential exoglycosidase treatment, all the IgG samples were found to contain a series of biantennary complex-type oligosaccharides. The incidenc e of galactose-free oligosaccharides was significantly higher in both IgGRF s and non-RF IgG from RA patients compared with IgG from healthy individual s. 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 w as the same as that of IgG from healthy individuals, In addition, the decre ases in galactosylation and sialylation of oligosaccharides in IgGRF correl ated well with the increase in RF activity. These findings could contribute to our understanding of the mechanisms of IgG-IgG complex formation and th e pathogenicity of these complexes in RA patients.