title: Histones interact with anionic phospholipids with high avidity; its relevance for the binding of histone-antihistone immune complexes.
abstract: Antibodies recognizing anionic phospholipids have been described in systemic lupus erythematosus (SLE) and other autoimmune diseases. Recent studies have shown that some of these antibodies may recognize a cardiolipin-binding protein (apolipoprotein H) rather than phospholipids. A similar possibility is conceivable for other cardiolipin-binding proteins that are targets of autoantibodies. In this study we have addressed whether this might be the case for histones, a set of highly cationic and widely distributed proteins that react in a well known autoantibody system. Our results indicate that: (i) histones bind to anionic phospholipids (cardiolipin and phosphatidylserine) with high avidity, but not to zwitterionic phospholipids (phosphatidylcholine); (ii) monoclonal and polyclonal antihistone antibodies recognize histones bound to cardiolipin; (iii) the addition of histones to serum samples containing antihistone antibodies often enhances their anticardiolipin reactivity. In addition, we have found that antihistone-producing hybridomas derived from MRL-lpr mice may show anticardiolipin activity due to the presence of histones in the cell culture supernatants with the resultant formation of immune complexes. Taken together, the results suggest a potential role for histones in the anti-cardiolipin activity detected in sera containing antihistone antibodies. These histone-phospholipid interactions should be taken into account when evaluating the pathogenic effects of antihistone antibodies or other autoantibodies reacting with nuclear components (e.g. nucleosomes) containing histones.
authors.affiliation: Department of Immunology, Hospital Universitario San Carlos, Madrid, Spain.
authors.forename: L F
authors.initials: LF
authors.lastname: Pereira
authors.forename: F M
authors.initials: FM
authors.lastname: Marco
authors.forename: R
authors.initials: R
authors.lastname: Boimorto
authors.forename: A
authors.initials: A
authors.lastname: Caturla
authors.forename: A
authors.initials: A
authors.lastname: Bustos
authors.forename: E G
authors.initials: EG
authors.lastname: De la Concha
authors.forename: J L
authors.initials: JL
authors.lastname: Subiza
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000915:Antibody Affinity / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000276:immunology*; D016736:Antiphospholipid Syndrome / Q000276:immunology; D001667:Binding, Competitive; D002308:Cardiolipins / Q000276:immunology; D005260:Female; D006657:Histones / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D010743:Phospholipids / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002308:Cardiolipins; D006657:Histones; D010743:Phospholipids