A comparative analysis of disease-associated changes in the galactosylation of serum IgG

Abstract

Serum IgG from patients with both adultand juvenile-onset rheumatoid arthritis when compared to age-matched controls has an increased prevalence of N-linked oligosaccharides whose outer arms lack galactose [G(O)] and terminate in Nacetylglucosamine. The reduction in galactosylation was found in lupus patients complicated by Sjogren’s syndrome but not in 85 patients with one of nine other rheumatological disorders, namely SLE, Sjogren’s syndrome (primary), myositis, scleroderma, osteoarthritis, psoriatic arthropathy, ankylosing spondylitis, postYersinia arthropathy, and gout. Further, this reduction in galactosylation was not simply concomitant with an acute or chronic inflammatory process, as shown by an analysis of the N-glycosylation of serum IgG from 84 patients with one or more than 13 different relevant disorders, namely klebsiella, leprosy, tuberculosis, rubella, parvovirus, mumps, glandular fever, AIDS, sarcoidosis, ulcerative colitis, Crohn’s multiple sclerosis, and Waldenstrom’s macroglobulinaemia. Of these, only serum IgG from patients with tuberculosis and Crohn’s disease had elevated G(0) values. Given the evidence for a major role of IgG autosensitization in the pathogenesis of rheumatoid arthritis, it is striking that this structural change in IgG carbohydrate, which may facilitate the self-association of IgG rheumatoid factors and contribute to autoantigenicity, should be restricted to such a small number of diseases. Human serum IgG is a glycoprotein [ 1, 21 carrying on average 2.8 N-linked oligosaccharides. Of these 2.0 are invariably located in the Fc (at the conserved Nglycosylation site of Asn 297), and additional ones in the variable region of the light and heavy chains, with a frequency and position dependent on the occurrence of the