STRUCTURAL-ANALYSIS OF THE N-GLYCANS FROM HUMAN-IMMUNOGLOBULIN A1 - COMPARISON OF NORMAL HUMAN SERUM IMMUNOGLOBULIN A1 WITH THAT ISOLATED FROM PATIENTS WITH RHEUMATOID-ARTHRITIS

The primary structures of the N-linked oligosaccharides from normal hu man serum IgA1 were determined by a combination of sequential exoglyco sidase digestion, Bio-Gel P-4 chromatography, anion-exchange chromatog raphy and one-dimensional n.m.r. spectroscopy. Three major N-linked di sialylated biantennary-complex-type structures were found (55%). The r emaining N-linked oligosaccharides consisted of at least nine further structures, some of which (7%) were of the triantennary type and inclu ded disialylated triantennary oligosaccharides with outer-arm fucose s ubstitution [Fuc alpha 1-3(4)]. Compared with IgG, the N-glycan struct ures on IgA are more completely processed: the outer arms have a highe r proportion of galactose and sialic acid, and only trace levels of in completely galactosylated oligosaccharides, commonly found on IgG, wer e detected. Analysis of the sialylated O-glycans revealed that 64% wer e [NeuAc2 alpha 3(6)](2)Gal beta 3GalNAc and 9% were [NeuAc2 alpha 3(6 )]-Gal beta 4GlcNAc beta 6[NeuAc2 alpha 3(6)Gal beta 3]GalNAc, and 27% were monosialylated. The N-linked glycosylation of both serum IgA1 an d IgG isolated from a group of six normal individuals was compared wit h that from ten patients with rheumatoid arthritis (RA). In contrast w ith the hypogalactosylation found in IgG from diseased sera, there was no evidence of an equivalent decrease in the galactosylation of the I gA1 oligosaccharides. In addition, the N-glycosylation of IgA1 was rem arkably consistent within the group of normal individuals. These data suggest that incomplete galactosylation of N-linked glycans and its au gmentation in RA does not extend to IgA1 and that the RA-associated ga lactosyltransferase deficiency may be restricted to cells producing ga mma-chain.