title: The complex role of DNA, histones and HMGB1 in the pathogenesis of SLE.
abstract: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by the production of antinuclear antibodies (ANA) in association with protean clinic manifestations. ANA can bind to nuclear molecules, most prominently DNA and histones in nucleosomes, to form complexes to promote pathogenesis. Because of the intrinsic immunological activity of the nuclear components, these complexes can amplify responses by interacting with diverse pattern recognition receptors and internal sensing systems. Among molecules associated with nucleosomal components, HMGB1, a non-histone protein, can emanate from activated and dying cells; HMGB1's immune activity is determined by post-translational modifications, redox state, and binding to other immune mediators. Although ANAs form complexes that deposit in the kidney or induce type 1 interferon, ANAs may also block immune activity. Together, these studies highlight the importance of complexes in the pathogenesis of lupus and their role as antigens, immunogens, and adjuvants.
authors.affiliation: Medical Research Service, Durham Veterans Administration Medical Center , Durham, NC , USA and.
authors.forename: David S
authors.initials: DS
authors.lastname: Pisetsky
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D004247:DNA / Q000276:immunology*; D024243:HMGB1 Protein / Q000276:immunology*; D006657:Histones / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D009707:Nucleosomes / Q000276:immunology
chemical_list: D000974:Antibodies, Antinuclear; D024243:HMGB1 Protein; D006657:Histones; D009707:Nucleosomes; D004247:DNA
keywords: Antinuclear antibody; DNA; HMGB1; histones; nucleosome; systemic lupus erythematosus