engleski

Serum Antibodies to Advanced Glycation Endproducts (AGE) and Circulating AGE-Immune Complexes in NIDDM Patients

Advanced glycation of protein causes their immunogenicity. In this study we investigated whether AGEs, as an antigen continuously formed in vivo, are recognized as an immunological epitope. The presence of circulating soluble immune complexes containing AGE moiety was tested as well. A blocking ELISA for the measurement of anti-AGE autoantibodies was developed. Serum AGE-immune complexes were detected by ELISA using an immunochemical bridge. Soluble AGE-IC were precipitated from serum by polyethylenglycol and analysed. Competitive ELISA was measured total serum AGEs. The autoantibody titer, expressed as percent of inhibition, was higher in the control group (n=20) than in NIDDM patients (n=64) (47.3 14.4 vs 26.0 11.8 %, p<0.001). To clarify whether AGE- autoantibodies are masked in vivo by immune complexes formation we determine immune complexes containing AGE as antigen. Circulating AGE-IC showed an inverse correlation with AGE level (r=-0.8, p<0.000). The content of AGE in soluble immune complexes was significantly higher in diabetic patients than in control subjects (3.51 1.9 vs 1.89 1.0  gEq/ml (p<0.00004), and correlate inversly with anti-AGE antibodies (r=-0.26, p<0.01). AGE autoantibody negativity was defined as a value lower than the mean of controls for 2SD. Antibody negative patients (48%) had a higher level of serum AGEs (14.4 6.2 vs 13.4 6.2  gEq/ml, p<0.001), longer diabetes duration (11 5 vs 9.9 6 yrs, p<0.01) and higher urinary albumin excretion (158 208 vs 79 176 mg/d, p<0.001) as compared to AGE antibody positive patients. Protein glycation and the ensuing autoimmune response lead to the generation of autoantibodies against AGE. Interactions of AGE autoantibodies with AGE as an antigen being continuously produced result in the formation of AGE-immune complexes that may play a role in the atherogenic processes.

advanced glycation products; antibody; immune complex

http://dx.doi.org/10.1016/S0168-8227(00)81217-6 ; DOI: 10.1016/S0168-8227(00)81217-6