ADVANCED GLYCATION ENDPRODUCTS (AGE) ON IGG, A TARGET FOR CIRCULATINGANTIBODIES IN NORTH-AMERICAN INDIANS WITH RHEUMATOID-ARTHRITIS (RA)

Several tribes of North American Indians are known to have poor glucos e control and are at a high risk of developing type 2 diabetes. Simila rly some tribes also exhibit RA at a high frequency. We have recently determined that a subset of Caucasian patients with RA mount an immune response to IgG modified with advanced glycation endproducts (AGE). T he AGE modifications on IgG in vivo include N-epsilon-(carboxymethyl) lysine, imidazolone and pentosidine. The presence of IgG-AGE and the a ntibody response to the IgG-AGE in the Ojibwe tribe of First Nations n ative Indians where both NIDDM and RA are prevalent was investigated. AGE modified IgG and albumin were determined using a modified nitroblu e tetrazolium assay. Rheumatoid factors (RFs) and IgM and IgA anti-IgG -AGE were detected by ELISA. Of the 108 individuals tested, 21 had RA only, 3 had both RA and type 2 diabetes, 30 had type 2 diabetes only a nd 51 had no diagnosed disease. AGE modified IgG was significantly ele vated in the RA group compared to the diabetic group. IgM and IgA RFs were detected in 83% and 50% of the RA patients, compared to 31-37% an d 7-10% of the diabetics or normal individuals. IgM anti-IgG-AGE was d etected in 54% of the RA patients, in contrast to 7-14% in the diabeti cs or normal individuals. IgA anti-IgG-AGE was detected in 42% of the RA patients and only 7 to 8% of the NIDDM or normal individuals. The I gM or IgA anti-IgG-AGE antibodies likely contribute to the accumulatio n of IgG-AGE, possibly through blocked clearance through AGE receptors . A trend towards more severe disease was seen in those Ojibwe RA pati ents with circulating anti-AGE antibodies. Non-enzymatic glycation may be an important pathogenic link in the RA seen in North American Indi ans.