A new antibody in rheumatoid arthritis targeting glycated IgG: IgM anti-IgG-AGE

Hyperglycaemia and/or oxidative stress can cause IgG to be modified by adva nced glycation end products (AGE). Three patients with aggressive rheumatoi d arthritis (RA) and vasculitis are described who have high titres of IgM a ntibodies against AGE-modified IgG (IgM anti-IgG-AGE). Diabetics and random ly selected patients with rheumatic diseases, including 50 additional RA pa tients, were tested for IgM and IgA anti-IgG-AGE by ELISA. AGE-modified pro teins were detected using the nitroblue tetrazolium (NBT) colorimetric meth od. The presence of NE (carboxymethyl) lysine, an AGE modification, was det ected on IgG-AGE by immunoblotting. A total of 20/41 (49%) rheumatoid facto r (RF)-positive RA patients tested had IgM anti-IgG-AGE antibodies, 4/12 (3 3%) RE-positive systemic lupus erythematosus (SLE) patients, 3/5 RF-positiv e patients with primary Sjogren's syndrome (SS), and 3/5 RF-positive diabet ics. All patients with RE-negative RA, SLE, SS, osteoarthritis (24), spondy loarthritis (15), adult-onset Still's disease (8), diabetes (25) and health y controls (20) were anti-IgG-AGE negative. RF and IgM anti-IgG-AGE appeare d to be a linked response. The IgM anti-IgG-ACE, along with IgG-AGE, may co ntribute to the pathogenesis of RA.