{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:36:53Z","timestamp":1790872613769,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,5,25]],"date-time":"2007-05-25T00:00:00Z","timestamp":1180051200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>In systemic lupus erythematosus (SLE), inadequate removal of apoptotic cells may lead to challenge of the immune system with immunogenic self antigens that have been modified during apoptosis. We undertook this study to evaluate whether apoptosis\u2010induced histone modifications are targets for the immune system in SLE.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The epitope of KM\u20102, a monoclonal antihistone autoantibody derived from a lupus mouse, was mapped by random peptide phage display. The reactivity of KM\u20102 and plasma with (acetylated) histone H4 (H4) peptides and with nonapoptotic, apoptotic, and hyperacetylated histones was determined by immunofluorescence staining, enzyme\u2010linked immunosorbent assay, and Western blotting.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>KM\u20102 recognized apoptosis\u2010induced acetylation of H4 at lysines 8, 12, and 16. The majority of plasma samples from SLE patients and lupus mice showed higher reactivity with triacetylated H4 peptide (residues 1\u201322) and with hyperacetylated and apoptotic histones than with nonacetylated H4 peptide and normal histones. Importantly, administration of triacetylated H4 peptide to lupus\u2010prone mice before disease onset accelerated the disease by enhancing mortality and aggravating proteinuria, skin lesions, and glomerular IgG deposition, while the nonacetylated H4 peptide had no pathogenic effect. The delayed\u2010type hypersensitivity response in lupus mice against the triacetylated H4 peptide was higher than that against the nonacetylated H4 peptide. Bone marrow\u2013derived dendritic cells (DCs) cultured in the presence of hyperacetylated nucleosomes showed increased expression\/production of CD40, CD86, interleukin\u20106 (IL\u20106), and tumor necrosis factor \u03b1 compared with DCs cultured in the presence of normal nucleosomes. Finally, DCs cultured in the presence of hyperacetylated nucleosomes were able to activate syngeneic T cells, because IL\u20102 production increased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Apoptosis\u2010induced acetylation of nucleosomes may represent an important driving force in the development of lupus.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22646","type":"journal-article","created":{"date-parts":[[2007,5,27]],"date-time":"2007-05-27T22:31:30Z","timestamp":1180305090000},"page":"1921-1933","source":"Crossref","is-referenced-by-count":114,"title":["Apoptosis\u2010induced acetylation of histones is pathogenic in systemic lupus erythematosus"],"prefix":"10.1002","volume":"56","author":[{"given":"J\u00fcrgen W.","family":"Dieker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin 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