Detection of autoantibodies against advanced glycation endproducts and AGE-immune complexes in serum of patients with diabetes mellitus.
Advanced glycation of protein causes their immunogenicity. The evidence that advanced glycation endproducts (AGEs) have antigenic properties has led to a hypothesis that the AGE structure found in vivo may exert an autoimmune response. In the present study, we showed the sera of diabetic patients as well as of nondiabetic individuals to contain autoantibodies to epitopes of AGE structures. Contrary to what might be expected, we observed lower AGE antibody titers in diabetic subjects, and postulated that the antibodies against AGEs form immune complexes in vivo, hampering their determination. The existence of immune complexes containing AGE moiety was established by two independent criteria: (a) serum AGE-immune complexes (AGE-IC) were detected by enzyme-linked immunosorbent assay (ELISA) using an immunochemical bridge; and (b) soluble AGE-IC were precipitated from serum by polyethylene glycol and analyzed. We demonstrated the presence of circulating AGE-IC in sera, predominantly in the sera of diabetic subjects. We also found an inverse correlation between serum AGE level and AGE-IC (r=-0.8, P<0.000), indicating the serum level of AGEs to decline with an increasing presence of AGE-IC. 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 microgEq/ml (P<0.00004), and correlated inversely with free antibodies (r=-0.26, P<0.01). Interactions of AGE autoantibodies with AGE as a continuously produced antigen result in the formation of AGE-immune complexes that may play a role in the atherogenic processes.
Turk
Z
Z
University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Dugi dol 4A, HR-10000 Zagreb, Croatia. zturk@indija.idb.hr
Ljubic
S
S
Turk
N
N
Benko
B
B
D000936:Antigen-Antibody Complex / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000276:immunology*; D006801:Humans
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D017127:Glycation End Products, Advanced