Adjuvant arthritis is associated with changes in the glycosylation of serum IgG1 and IgG2b.
The increased amounts of agalactosyl IgG (N-linked oligosaccharides terminating with N-acetylglucosamine (GlcNAc) in the serum of patients with rheumatoid arthritis (RA) and other chronic inflammatory diseases have suggested that agalactosyl IgG may be involved in the pathogenesis of RA. We have now evaluated the incidence of agalactosyl IgG in the Lewis rat during the course of adjuvant arthritis (AA). The modification in glycosylation of IgG was measured by means of polyclonal and monoclonal anti GlcNAc antibodies as well as by the lectin concanavalin A (Con A). The results show that Lewis rats undergo a change in serum IgG glycosylation during the course of AA. As in human RA patients, rats with AA lack terminal galactose on IgG heavy chain oligosaccharides, and the terminal GlcNAc or mannose residues are thus exposed. The degree of agalactosyl IgG was positively correlated with the incidence of disease, peaked 20 days after disease induction, and the IgG gradually reverted to the fully glycosylated form thereafter. The post-arthritic glycosylation profile was very similar to that characteristic of the naive animal. Purified IgG was shown to contain two IgG subclasses, IgG1 and IgG2b, which underwent changes in glycosylation. Western blot analysis revealed that IgG1 expressed a higher degree of terminal mannose, whereas IgG2b expressed a higher degree of terminal GlcNAc. These findings raise the question of the possible involvement of agalactosyl IgG in immune complex-mediated inflammation.
Yagev
H
H
Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot, Israel.
Frenkel
A
A
Cohen
I R
IR
Friedman
A
A
D000117:Acetylglucosamine / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal; D001169:Arthritis, Experimental / Q000097:blood / Q000276:immunology*; D015153:Blotting, Western; D003208:Concanavalin A / Q000276:immunology; D005690:Galactose / Q000378:metabolism; D006031:Glycosylation; D007074:Immunoglobulin G / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011863:Radioimmunoassay; D051381:Rats; D011917:Rats, Inbred Lew; D013297:Streptococcus pyogenes / Q000276:immunology
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D003208:Concanavalin A; D000117:Acetylglucosamine; D005690:Galactose