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).
|Titolo:||Antiphospholipid antibodies mediate autoimmunity against dying cells|
|Parole Chiave:||Anti-domain antibodies; Antiphospholipid antibodies; Antiphospholipid syndrome; Autoantibodies; Beta2glycoprotein I; Systemic lupus erythematosus; Animals; Antibodies, Antiphospholipid; Apoptosis; Autoantibodies; Autoimmunity; Cell Death; Disease Models, Animal; Humans; beta 2-Glycoprotein I; Immunology and Allergy; Immunology|
|Settore Scientifico Disciplinare:||Settore MED/16 - Reumatologia|
|Data di pubblicazione:||2013|
|Digital Object Identifier (DOI):||10.3109/08916934.2013.783025|
|Appare nelle tipologie:||01 - Articolo su periodico|