Abstract
Advanced glycation end-products (AGEs) have been found to be critically involved in initiation or progression of diabetes secondary complications (nephropathy, retinopathy, neuropathy, and angiopathy). Various hyper-glycating carbonyl compounds such as 3-deoxyglucosone (3-DG) are produced in pathophysiological conditions that form AGEs in high quantity both in vivo and in vitro. In the first stage of this study, we glycated histone H2A protein by 3-DG, and the results showed the formation of various intermediates and AGEs as well as structural changes in the protein. In the second stage, we studied the immunogenicity of native and 3-DG-glycated H2A protein in female rabbits. The modified H2A was highly immunogenic, eliciting high titer immunogen-specific antibodies, while the unmodified form was almost nonimmunogenic. Antibodies against standard carboxymethyllysine (CML) and pentosidine were detected in the immunized female rabbits, which demonstrates the immunogenic nature of AGEs (CML and pentosidine) as well. The results show both structural perturbation and AGEs have the capacity of triggering the immune system due to the generation of neoepitopes that render the molecule immunogenic. This study shows the presence of autoantibodies against 3-DG-modified H2A, CML, and pentosidine in the sera of type 2 diabetes patients having secondary complications. Autoantibodies against damaged H2A and AGEs may be significant in the assessment of initiation/progression of secondary complications in type 2 diabetes mellitus patients or may be used as a marker for early detection of secondary complications in diabetes.