Prolonged incubation of proteins with reducing sugar produces advanced glycation end products (AGEs), which are implicated as factors for aging and diabetic complications. We previously demonstrated the presence of N(epsilon)-(carboxymethyl)lysine (CML), one of the main AGE structures, in human and animal tissues using a monoclonal anti-CML antibody (6D12). These findings suggest that CML structures present in vivo could serve as immunogens to generate autoantibodies. This suggestion was tested in the present study. First, plasma samples from diabetic rats reacted positively with AGE bovine serum albumin (BSA). These reactivities increased with the duration of diabetic states and were inhibited specifically by CML-BSA. Second, a fraction purified from plasma of diabetic patients, which bound to AGE-BSA, showed a positive reaction to CML-BSA and furthermore also to human lens proteins, which are known to undergo CML modification in vivo. Finally, patients with renal failure caused by diabetes or nondiabetic pathologies had a higher autoantibody activity against CML structure than that in normal subjects or diabetic patients without renal failure. These results indicate that CML accumulated in vivo serves as an immunological epitope to generate an autoantibody specific for CML that might be used as a potential marker for diabetic nephropathy or chronic renal failure.

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