engleski

Autoantibodies against advanced glycation endproducts in IDDM

Advanced glycation process is one of the main pathogenic mechanisms linked to the development of diabetic sequels. The evidence that AGEs have antigenic properties led to a hypothesis that AGE as an antigen continuously formed in a diabetic body may arouse an autoimmune response. The incidence of serum antibodies to AGEs and AGE levels was assessed in 97 IDDM patients and 26 age-matched healthy controls. AGE antibody titer was defined as a ratio of antibody binding to AGE- modified HSA versus binding to unmodified HSA (human serum albumin) using a solid phase ELISA. A purified immunoglobulin fraction from human plasma (1660 healthy donors) of normal subclass distribution was used as a standard. By means of immunoassay, we assessed the antibody ratio and AGE levels in the serum of healthy volunteers (1.27?0.13 ; AGE=14.1?1.9 U/mg ; n=26) (mean?SD), newly-detected IDDM (1.21?0.17 ; AGE=27.7?6.1 U/mg ; HbA1c=12.8?4.4% n=21), IDDM patients with (0.91? 0.2 ; AGE=31.4?7.9 U/mg ; HbA1c=9.4?2.7% n=27) and withouth (1.07?0.2 ; AGE=33.0?7.1 U/mg ; HbA1c=9.5? 3.1% n=27) microangiopathy, and diabetic patients with end stage renal disease (ESRD) (0.81?0.1 ; AGE=24.6?3.8 U/mg ; n=22). In patients with clinically established retinopathy and/or nephropathy the antibody ratio was lower than in patients without complications (0.86?0.2 vs 1.14? 0.2, p<0.001), irrespectively of their glycemic status. The antobody ratio did not correlate with either HbA1c or serum AGEs. Diabetes duration was a major correlating factor (r=0.3, p<0.001), but there was no correlation with age. AGE levels correlated significantly with HbA1c (r=0.6, p<0.001) in all patient groups. These data indicate an autoimmune response of diabetic subjects to the proteins modified by advanced glycation. Long-term presence of both antigens and antigen-specific antibodies might be the cause of a series of undesired phenomena. There is possibility that AGE antibodies form immune complexes, which are believed to have a role in atherogenesis. Therefore, additional studies are needed to establish the role and significance of autoantibodies against AGE in atherogenic processes in diabetes.

advanced glycation endproduct; autoantibodies; diabetes

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