title: 4-Hydroxy-2-nonenal modified histone-H2A: a possible antigenic stimulus for systemic lupus erythematosus autoantibodies.
abstract: 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<0.0001). Furthermore, HNE-H2A was also detected in SLE peripheral blood mononuclear cells. In conclusion, this is the first study to demonstrate the role of HNE-modified-histone in SLE. Preferential binding of HNE-H2A by affinity purified SLE-IgG pointed out the likely role of HNE-H2A in the initiation/progression of SLE.
authors: Department of Dermatology, College of Medicine, Qassim University, Buraidah 51452, Saudi Arabia.
authors: Abdullateef A
authors: AA
authors: Alzolibani
authors: Ahmad A
authors: AA
authors: Al Robaee
authors: Hani A
authors: HA
authors: Al-Shobaili
authors: Zafar
authors: Z
authors: Rasheed
mesh_terms: D000293:Adolescent; D000328:Adult; D000447:Aldehydes / Q000037:antagonists & inhibitors / Q000276:immunology*; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D001667:Binding, Competitive; D015153:Blotting, Western; D016022:Case-Control Studies; D000939:Epitopes / Q000276:immunology; D005260:Female; D006657:Histones / Q000097:blood / Q000276:immunology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D015227:Lipid Peroxidation; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011817:Rabbits; D055815:Young Adult
chemical_list: D000447:Aldehydes; D001323:Autoantibodies; D000939:Epitopes; D006657:Histones; C027576:4-hydroxy-2-nonenal
keywords: 4-Hydroxy-2-nonenal; Autoimmunity; HNE-H2A; Histone-H2A; Nucleoprotein; SLE