Rheumatoid arthritis, glycosylation

Kineret is the tradename given to a recently approved product based on the latter strategy. Indicated in the treatment of rheumatoid arthritis, the product consists of a recombinant form of the human IL-1 receptor antagonist. The 17.3 kDa, 153 amino acid product is produced in engineered E. coli and differs from the native human molecule in that it is non-glycosylated and contains an additional N-terminal methionine residue (a consequence of its prokaryotic expression system). 

Backlund, J, Carlsen, S, Hdger, T, Hohn, B, Eugger, L, Kihlberg, J, Burkhardt, H, Holmdahl, R, Predominant selection of T cells specific for the glycosylated collagen t)fpe II epitope (263-270) in humanized transgenic mice and in rheumatoid arthritis, Proc. Natl. Acad. Sci. USA, 99,9960-9965, 2002. 

The molecular basis of inherited defects is established for a number of diseases and altered glycosylation patterns have been observed to be associated with these. For example, IgG Fc fragment conserved site glycans lacking in outer arm Gal residues increase in rheumatoid arthritis, tuberculosis and Crohn s disease. There is also an Fab-specific increase in glycans bearing a bisecting Gn and a core Fuc [148]. 

Acute phase proteins are plasma proteins produced mainly by hepatocytes. Most APPs are glycoproteins with one or more N-linked complex glycans. Stimulants that commonly induce the acute phase response include tissue injury, rheumatoid arthritis, bacterial infection, inflammation, and neoplasms. Cytokines, notably interleukin-6, induce striking alterations in the concentration and glycosylation pattern of APPs in response to these stimuli [160]. 

Serum and synovial fluid have been obtained at the same time from 22 patients with rheumatoid arthritis and analyzed for microheterogeneity of a 1-acid-glycoprotein [16]. In most samples the glycosylation pattern was similar, a nonreactive variant and two Con A reactive variants (the first and the second). In seven samples of synovial fluid an extra third peak was observed representative of the fraction strongly reactive with Con A. 

Immunoglobulin G Glycosylation and Galactosyltransferase Changes in Rheumatoid Arthritis... 

Are the Rheumatoid Arthritis Associated Glycosylation Abnormalities Unique ... 

Parekh RB, Dwek RA, Sutton BJ et al. Association of rheumatoid arthritis and primary osteoarthritis with changes in the glycosylation pattern of total serum IgG. Nature (1985) 316 452-457. 

Alavi A, Arden N, Spector TD Axford JS. IgG glycosylation changes are associated with the clinical outcome of rheumatoid arthritis in pregnancy. Arth Rheum 1997 40(9) Suppl. S149 No. 771. 

Alavi A, Axford JS, Hay FC, Jones MG. Tissue-specific galactosyltransferase abnormalities in an experimental model of rheumatoid arthritis. Ann Med Intern (1998) 149(5) 251-260. Axford JS, Sumar N, Alavi A, Isenberg DA, Young A, Bodman KB, Roitt IM. Changes in normal glycosylation mechanisms in autoimmune rheumatic disease. J Clin Invest (1992) 89(3) 1021-1031. 

Malhotra, R, Wormald, M.R., Rudd, P.M., Fischer, P.B., Dwek, R.A. (1995) Glycosylation changes of IgG associated with rheumatoid arthritis can activate complement via the mannosebinding protein. Nature Medicine, 1, 237-241. 

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