An autoantibody targeting glycated IgG is associated with elevated serum immune complexes in rheumatoid arthritis (RA).
Advanced glycation end-products (AGE) play a role in diabetes complications and in RA. An autoantibody to IgG-AGE has been shown to correlate with RA disease activity. Thus we sought to analyse serum immune complexes (IC) and AGE-modified proteins in Caucasians and North American Indians to see if the presence of anti-IgG-AGE influenced their composition. Polyethylene glycol precipitation of IC from the serum of anti-IgG-AGE-positive or -negative RA patients, and healthy and diabetic controls were examined. Concentrations of circulating IC were highest in anti-IgG-AGE+ RA patients, followed by anti-IgG-AGE- RA patients, which were greater than healthy controls. IC amounts in the Ojibwe were consistently higher than in Caucasians. Affinity purification of AGE-modified proteins from IC and immunoblotting with antibodies against Ig gamma and mu heavy chains, kappa and lambda light chains, and AGE Nepsilon(carboxymethyl)lysine and imidazolone yielded similar results: anti-AGE+ RA patients had elevated levels relative to those without the autoantibody. Levels in both RA groups were higher than in controls. Glycated albumin amounts followed a similar distribution, but were not influenced by the presence of anti-AGE antibodies. A heavily glycated kappa-chain was present primarily in IC from anti-IgG-AGE+ patients. These studies indicate that anti-AGE antibodies have a direct impact on the accumulation of IgG-AGE but not glycated albumin, and may block the normal clearance of IgG-AGE through AGE receptors.
Tai
A W
AW
Division of Rheumatology, Montreal General Hospital, Montreal General Hospital Research Institute, McGill University, Montreal, QC, Canada.
Newkirk
M M
MM
D000888:Antibodies, Anti-Idiotypic / Q000097:blood* / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D017127:Glycation End Products, Advanced / Q000097:blood* / Q000276:immunology; D006801:Humans; D007198:Indians, North American; D044465:White People
D000888:Antibodies, Anti-Idiotypic; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D017127:Glycation End Products, Advanced; C048844:anti-IgG