Rheumatoid arthritis (RA) is a widely prevalent (1–3%) chronic systemic disease thought to have an autoimmune component1; both humoral1–4 and cellular5,6 mechanisms have been implicated. Primary osteoarthritis (OA) is considered to be distinct from rheumatoid arthritis, and here damage is thought to be secondary to cartilage degeneration. In rheumatoid arthritis, immune complexes are present that consist exclusively of immunoglobulin7, implying that this is both the ‘antibody’ (rheumatoid factor [RF]) and the ‘antigen’ (most commonly IgG). Autoantigenic reactivity has been localized to the constant-region (Cγ2) domains of IgG8, 9. There is no evidence for a polypeptide determinant but carbohydrate changes have been reported10. We have therefore conducted a study, simultaneously in Oxford and Tokyo, to compare in detail the N-glycosylation pattern of serum IgG (Fig. 1) isolated from normal individuals and from patients with either primary osteoarthritis or rheumatoid arthritis. The results, which required an evaluation of the primary sequences of ∼1,400 oligosaccharides from 46 IgG samples, indicate that: (1) IgG isolated from normal individuals, patients with RA and patients with OA contains different distributions of asparagine-linked bi-antennary complex-type oligosaccharide structures, (2) in neither disease is the IgG associated with novel oligosaccharide structures, but the observed differences are due to changes in the relative extent of galactosylation compared with normal individuals. This change results in a ‘shift’ in the population of IgG molecules towards those carrying complex oligosaccharides, one or both of whose arms terminate in N-acetylglucosamine. These two arthritides may therefore be glycosylation diseases, reflecting changes in the intracellular processing, or post-secretory degradation of N-linked oligosaccharides.
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Parekh, R., Dwek, R., Sutton, B. et al. Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature 316, 452–457 (1985). https://doi.org/10.1038/316452a0
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