Advanced glycation end-product (AGE)-damaged IgG and IgM autoantibodies to IgG-AGE in patients with early synovitis.
Advanced glycation end-product (AGE)-damaged IgG occurs as a result of hyperglycemia and/or oxidative stress. Autoantibodies to IgG-AGE were previously demonstrated in patients with severe, longstanding rheumatoid arthritis (RA). We investigated whether IgG-AGE and anti-IgG-AGE antibodies were present early in the course of RA and other inflammatory arthropathies. We prospectively followed a cohort of 238 patients with inflammatory arthritis of duration less than 1 year. Patients were evaluated clinically and serologically, and radiographs were obtained at initial and 1-year visits. Sera were assayed for IgG-AGE and anti-IgG-AGE antibodies by enzyme-linked immunosorbent assay (ELISA). Rheumatoid factor (RF) was determined by nephelometry and ELISA. Of all patients, 29% had RF-positive RA, 15% had RF-negative RA, 18% had spondyloarthropathy, and 38% had undifferentiated arthritis. IgG-AGE was present in 19% of patients, and was similar in amount and frequency in all groups. Patients with elevated IgG-AGE levels had significantly higher levels of the inflammatory markers C-reactive protein and erythrocyte sedimentation rate, but there was no correlation with blood glucose levels. Overall, 27% of the patients had IgM anti-IgG-AGE antibodies. These antibodies were highly significantly associated with RFs (P < 0.0001) and with swollen joint count (P < 0.01). In early onset arthritis, IgG damaged by AGE was detected in all patient groups. The ability to make IgM anti-IgG-AGE antibodies, however, was restricted to a subset of RF-positive RA patients with more active disease. The persistence of the anti-IgG-AGE response was more specific to RA, and was transient in the patients with spondyloarthropathy and with undifferentiated arthritis who were initially found to be positive for anti-IgG-AGE antibodies.
Newkirk
Marianna M
MM
McGill University Health Centre, Montreal, Quebec, Canada. Marianna.Newkirk@mcgill.ca
Goldbach-Mansky
Raphaela
R
Lee
Jennifer
J
Hoxworth
Joseph
J
McCoy
Angie
A
Yarboro
Cheryl
C
Klippel
John
J
El-Gabalawy
Hani S
HS
D000328:Adult; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D005260:Female; D017127:Glycation End Products, Advanced / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007075:Immunoglobulin M / Q000097:blood* / Q000276:immunology; D046911:Macromolecular Substances; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013585:Synovitis / Q000175:diagnosis / Q000276:immunology*
D001323:Autoantibodies; D017127:Glycation End Products, Advanced; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D046911:Macromolecular Substances