Glycoxidation of histone proteins in autoimmune disorders

Post translational modifications (PTMs) alter the characteristic properties of proteins by influencing the spatial orientation of amino acid residues leading to a variety of pathological complications. Among the large number of PTMs, much attention has focused on non-enzymatic glycation and oxidation of proteins that form advanced glycation end products and generate autoantibodies. Histone proteins are essential components of chromatin structure and have role in its higher order structural formation. They have abundance of lysine and arginine residues and thus are prone to glyoxidation reactions. Glyoxidation causes structural alterations in histones and consequently leads to a variety of modifications in their amino acid sequence and the secondary and tertiary structure producing new antigenic determinants that may result in cause an aggressive autoimmune response. Here we review and evaluate the field of histone glyoxidation and its role in autoimmune disorders. We explore their structural alterations and immunogenicity of histones after glycation and oxidation reactions, and their role in autoimmune disease such as systemic lupus erythematosus, rheumatoid arthritis and diabetes.