Antiphospholipid antibodies mediate autoimmunity against dying cells. (August 2013)

• Record Type: Journal Article
• Authors: Andreoli, Laura; Fredi, Micaela; Nalli, Cecilia; Franceschini, Franco; Meroni, Pier Luigi; Tincani, Angela
• Is Part Of: Autoimmunity. Volume 46:Number 5(2013)
• Page Start: 302
• Page End: 306
• Publication Date: 2013-08
• Subjects: Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; 571.973
• DOI: 10.3109/08916934.2013.783025
• Languages: English
• ISSNs: 0891-6934

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <p>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 β2GPIand the activation ofβ2GPI-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).</p> </abstract>