Long-term incubation of proteins with reducing sugar proceeds to advanced glycation end products (AGEs). We previously demonstrated the presence of AGE structures in human and animal tissues, and suggested the implication of AGEs in aging and diabetic complications. In this study, we tested whether AGEs present in vivo, such as Nε-(carboxymethyl) lysine (CML) adduct, could serve as immunogens for generating autoantibodies. Plasma samples from STZ-induced diabetic rats reacted positively with AGE-proteins as well as CML-BSA, suggesting the presence of autoantibodies against AGE-structures, particularly CML in diabetic rats; the activity of the autoantibody increased with the duration of diabetic states, reflecting the accumulation of AGE proteins in these diabetic rats. An autoantibody fraction purified from the plasma of diabetic patients showed a positive reaction to AGE-proteins as well as to CML proteins, and also to human lens proteins which are known to undergo CML modification in vivo. Patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against AGE structures than that in normal subjects or diabetic patients without renal failure. These results suggest that AGEs accumulated in vivo serve as immunological epitopes for developing autoantibodies against AGEs, particularly against a CML structure, which might be used as an indicator of diabetic nephropathy or chronic renal failure.
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