4-Hydroxy-2-nonenal modified histone-H2A: A possible antigenic stimulus for systemic lupus erythematosus autoantibodies

•This study demonstrates the role of HNE-modified-histone in SLE.•Modification in H2A by HNE caused alteration in histidine, lysine and cystein.•HNE-induced epitopes on histone-H2A are strongly recognized by SLE-IgG. Protein modifications by 4-hydroxy-2-nonenals (HNE) are involved in various diseases. Histones are DNA protective nucleoprotein, which adopt different structures under oxidative stress. This study was undertaken to test the role of HNE-modified-histone-H2A (HNE-H2A) in systemic lupus erythematosus (SLE). Our data revealed that HNE-mediated-lipid peroxidation in histone-H2A caused alteration in histidine, lysine and cystein residues. In addition, protein carbonyl contents were also high in HNE-H2A. HNE-specific quencher, L-carnosine further reiterates HNE-modifications. Specificity of autoantibodies from SLE patients (n=48) were analyzed towards HNE-H2A and their results were compared with sex- and age-matched controls (n=36). SLE autoantibodies show preferential binding to HNE-H2A in comparison with histone-H2A (p