title: Antiphospholipid antibodies mediate autoimmunity against dying cells.
abstract: The Antiphospholipid Syndrome (APS) is characterized by thrombosis and pregnancy loss, clinical events mediated by pathogenic anti-phospholipid autoantibodies (aPL). β2-glycoprotein I (β2GPI) is the major autoantigens recognized by aPL. β2GPI is a cationic protein that binds to negatively charged surfaces such as those of apoptotic cells. This feature may lead to two major events: i) immunization with β2GPI fosters the Fc-receptor-mediated uptake by antigen presenting cells of apoptotic material decorated with β2GPI and the activation of β2GPI-specific T cells which in turn provide help to β2GPI-specific B cells for the production of anti-β2GPI; ii) apoptotic bodies decorated with β2GPI can be opsonized by anti-β2GPI and shifted towards a pro-inflammatory clearance by macrophages; epitope spread can occur with the generation of autoimmunity against nuclear autoantigens. In the presence of a predisposing genetic background and of a particular cytokine environment (type I interferons), the sequential emergence of autoantibodies can evolve into overt clinical disease. The spectrum of clinical phenotypes of the patients can be modulated by several factors affecting the pathogenicity of anti-β2GPI (e.g. domain specificity). We conclude that dying cells may play a dual role in APS: (I) as immunogen for the induction of aPL (etiology) and (II) as targets of aPL for the chronification of inflammation and the development of autoimmune diseases (pathology).
authors.affiliation: Rheumatology and Clinical Immunology, Spedali Civili and University of Brescia, Italy. andreoli@bresciareumatologia.it
authors.forename: Laura
authors.initials: L
authors.lastname: Andreoli
authors.forename: Micaela
authors.initials: M
authors.lastname: Fredi
authors.forename: Cecilia
authors.initials: C
authors.lastname: Nalli
authors.forename: Franco
authors.initials: F
authors.lastname: Franceschini
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Meroni
authors.forename: Angela
authors.initials: A
authors.lastname: Tincani
mesh_terms: D000818:Animals; D017152:Antibodies, Antiphospholipid / Q000096:biosynthesis / Q000502:physiology*; D017209:Apoptosis / Q000235:genetics / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D016923:Cell Death / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D053482:beta 2-Glycoprotein I / Q000096:biosynthesis / Q000276:immunology
chemical_list: D017152:Antibodies, Antiphospholipid; D001323:Autoantibodies; D053482:beta 2-Glycoprotein I