title: Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in SLE patients: glycated-histones as likely trigger for SLE?
abstract: Histones are the most abundant proteins associated with genomic DNA. Recent observations show that histones are quite susceptible to non-enzymatic glycation which results in the generation of free radicals causing structural perturbations. In this study, our aim is to define the role of deoxyribose-modified H2A histone in SLE initiation/progression. Glycation reaction was carried out by incubating H2A histone with 10 mM deoxyribose for 21 days at 37 °C. Structural changes in glycated-H2A were studied by various physico-chemical techniques. The antigen-antibody interaction was studied by direct binding, inhibition ELISA and mobility shift assay. Deoxyribose-modified-H2A histone showed increased hyperchromicity and increased fluorescence intensity. CD results demonstrated almost 50% loss in alpha helix conformation as a consequence of glycation. This was supported by an increase in Tm value vis-à-vis thermal stability. Glycated-H2A showed cross linking in SDS-PAGE. SLE sera positive for anti-nDNA autoantibodies showed preference for deoxyribose-modified-H2A histone compared to native H2A histone or native DNA. Inhibition ELISA supported the above findings. Band shift assay further reiterated the preferential recognition of glycated-H2A over native H2A by SLE IgG autoantibodies. Deoxyribose-modified-H2A histone exhibited damage as revealed by various physico-chemical studies. Glycation of H2A has resulted in the generation of neo-epitopes on H2A histone, which are preferably bound by SLE anti-nDNA autoantibodies. It implies that deoxyribose-modified-H2A may trigger immune response resulting in the generation of anti-glycated H2A antibodies with DNA cross reacting properties.
authors: Department of Biochemistry, Faculty of Medicine , A.M.U., Aligarh, Uttar Pradesh , India and.
authors: Sana
authors: S
authors: Alam
authors: Zarina
authors: Z
authors: Arif
authors: Khursheed
authors: K
authors: Alam
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D000974:Antibodies, Antinuclear / Q000737:chemistry* / Q000378:metabolism; D000936:Antigen-Antibody Complex / Q000737:chemistry* / Q000378:metabolism; D001667:Binding, Competitive; D016022:Case-Control Studies; D002417:Cattle; D004247:DNA / Q000737:chemistry; D003855:Deoxyribose / Q000737:chemistry; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006031:Glycosylation; D006657:Histones / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry* / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D011485:Protein Binding; D055550:Protein Stability; D017433:Protein Structure, Secondary
chemical_list: D000974:Antibodies, Antinuclear; D000936:Antigen-Antibody Complex; D006657:Histones; D007074:Immunoglobulin G; D003855:Deoxyribose; D004247:DNA; C427203:calf thymus DNA
keywords: AGEs; SLE; anti-DNA antibodies; deoxyribose; glycated histone