title: A single-stranded DNA-cross-reactive immunogenic epitope of human homocysteine-inducible endoplasmic reticulum protein.
abstract: The mechanism involved in generating anti-DNA antibodies (Abs) remains unclear, as DNA is poorly immunogenic. Molecular mimicry between DNA and non-DNA substances has been implicated as a possible mechanism. We previously reported that homocysteine-inducible endoplasmic reticulum protein (Herp), which is induced by endoplasmic reticulum stress, is recognized by anti-double-stranded DNA (dsDNA) IgG from patients with systemic lupus erythematosus and that immunization with Herp elicits anti-dsDNA Abs in BALB/c mice. In this study, we observed that anti-single-stranded DNA (ssDNA) Abs were also generated in Herp-immunized BALB/c mice and established an anti-Herp monoclonal antibody (mAb), HT4, which specifically cross-reacted with ssDNA. The epitope of the HT4 mAb on Herp, 'EPAGSNR', was identified by screening a synthetic peptide library. The binding of the HT4 mAb to the peptide was competitively inhibited by ssDNA. Immunization of the epitope peptide elicited anti-ssDNA Abs in BALB/c mice. These results indicate that the epitope exists in a human self-protein, mimics ssDNA and shows antigenicity for anti-ssDNA Abs in normal mice. Anti-ssDNA Abs are often found in patients with drug-induced lupus erythematosus. Treatment with representative drugs that cause drug-induced lupus (chlorpromazine, procainamide and hydralazine) induced Herp expression and apoptosis in HeLa cells. These findings suggest that molecular mimicry between Herp and ssDNA is involved in anti-ssDNA Ab production in drug-induced lupus.
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Rheumatology, Yokohama Rosai Hospital, Yokohama, JapanDepartment of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Rheumatology, Yokohama Rosai Hospital, Yokohama, JapanDepartment of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hirabayashi
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Rheumatology, Yokohama Rosai Hospital, Yokohama, JapanDepartment of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ikeda
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Rheumatology, Yokohama Rosai Hospital, Yokohama, JapanDepartment of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fujii
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Rheumatology, Yokohama Rosai Hospital, Yokohama, JapanDepartment of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.affiliation: Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, JapanDepartment of Rheumatology, Yokohama Rosai Hospital, Yokohama, JapanDepartment of Rheumatology, Hikarigaoka Spellman Hospital, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Harigae
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis; D001323:Autoantibodies / Q000276:immunology*; D045744:Cell Line, Tumor; D003429:Cross Reactions; D004247:DNA / Q000276:immunology*; D004277:DNA, Single-Stranded / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006367:HeLa Cells; D006710:Homocysteine / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000139:chemically induced* / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D001323:Autoantibodies; D004277:DNA, Single-Stranded; D000939:Epitopes; C485932:HERPUD1 protein, human; D007074:Immunoglobulin G; D008565:Membrane Proteins; D006710:Homocysteine; D004247:DNA