Acta NaturaeActa NaturaeActa Naturae2075-8251Acta Naturae Ltd1081410.32607/20758251-2009-1-2-66-72ArticlesСтатьиResearch ArticleCovalent Binding Antibodies Suppress Advanced glycation: On the Innate Tier of Adaptive ImmunityCovalent Binding Antibodies Suppress Advanced glycation: On the Innate Tier of Adaptive ImmunityShcheglovaTMakkerS PTramontanoAtramontano@ucdavis.eduInstitute of Cytology and Genetics, Siberian Branch of the Russian Academy of SciencesDepartment of Pediatrics, University of California, Davis – School of Medicine Davis1509200912NO2 (2009)№2 (2009)667217012020Copyright ©; 2009, Shcheglova T., Makker S.P., Tramontano A.Copyright ©; 2009, Shcheglova T., Makker S.P., Tramontano A.2009Shcheglova T., Makker S.P., Tramontano A.Shcheglova T., Makker S.P., Tramontano A.https://creativecommons.org/licenses/by/4.0https://actanaturae.ru/2075-8251/article/view/10814

Non-enzymatic protein glycation is a source of metabolic stress that contributes to cytotoxicity and tissue damage. Hyperglycemia has been linked to elevation of advanced glycation endproducts, which mediate much of the vascular pathology leading to diabetic complications. Enhanced glycation of immunoglobulins and their accelerated vascular clearance is proposed as a natural mechanism to intercept alternative advanced glycation endproducts, thereby mitigating microvascular disease. We reported that antibodies against the glycoprotein KLH have elevated reactivity for glycopeptides from diabetic serum. These reactions are mediated by covalent binding between antibody light chains and carbonyl groups of glycated peptides. Diabetic animals that were immunized to induce reactive antibodies had attenuated diabetic nephropathy, which correlated with reduced levels of circulating and kidney-bound glycation products. Molecular analysis of antibody glycation revealed the preferential modification of light chains bearing germline-encoded lambda V regions. We previously noted that antibody fragments carrying V regions in the germline configuration are selected from a human Fv library by covalent binding to a reactive organophosphorus ester. These Fv fragments were specifically modified at light chain V region residues, which map to the combining site at the interface between light and heavy chains. These findings suggest that covalent binding is an innate property of antibodies, which may be encoded in the genome for specific physiological purposes. This hypothesis is discussed in context with current knowledge of the natural antibodies that recognize altered self molecules and the catalytic autoantibodies found in autoimmune disease.

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