Circulating autoantibodies in cancer patients have high specificity for glycoxidation modified histone H2A

• Methylglyoxal mediated glyoxidation enhances melting temperature of histone H2A.
• MG-H2A shows amorphous aggregate formation under electron microscope.
• MG-H2A is highly immunogenic and induces specific immune response.
• Circulating autoantibodies against MG-H2A were found in sera of cancer patients.
• AGEs and cancer are thus linked and may be significant for biomarker development.

BackgroundNovel immunological epitopes upon glyoxidation modified proteins have been discovered and multi-specific natural antibodies against them have been identified. The association of glyoxidation with cancer has also been reported. We probed the link of glyoxidation of histone H2A with autoimmune response in cancer.MethodsWe report the formation of thermo stable amorphous aggregate formation in histone H2A upon methylglyoxal modification using circular dichroism (CD) analysis and transmission electron microscopy.ResultsThe modified histone was found to be highly immunogenic that generates specific immune response in rabbits as analysed by cross reaction studies by competitive ELISA and Western blotting technique. The anti-methylglyoxal modified H2A antibodies were found in the circulating autoantibodies in various types of cancer patients by immunosorbent assay and gel retardation studies. The results clearly indicate the formation of highly specific antibodies in cancer patients against glyoxidation modified histone H2A with cross reactive tendencies with other glycated proteins and nucleic acids.ConclusionsThe results are important because a link between AGE–RAGE axis (Advanced glycation end products and Receptors for AGEs) and carcinogenesis is emerging and the role of glyoxidation of proteins is expected in the development of biomarkers for the early detection of cancer.