Journal
AUTOIMMUNITY
Volume 46, Issue 5, Pages 302-306Publisher
INFORMA HEALTHCARE
DOI: 10.3109/08916934.2013.783025
Keywords
Antiphospholipid antibodies; beta2glycoprotein I; anti-domain antibodies; antiphospholipid syndrome; systemic lupus erythematosus; autoantibodies
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Funding
- Government of Lombardy
- University of Brescia
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The Antiphospholipid Syndrome (APS) is characterized by thrombosis and pregnancy loss, clinical events mediated by pathogenic anti-phospholipid autoantibodies (aPL). beta 2-glycoprotein I (beta 2GPI) is the major autoantigens recognized by aPL. beta 2GPI 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 beta 2GPI fosters the Fc-receptor-mediated uptake by antigen presenting cells of apoptotic material decorated with beta 2GPIand the activation of beta 2GPI-specific T cells which in turn provide help to beta 2GPI-specific B cells for the production of anti-beta 2GPI; ii) apoptotic bodies decorated with beta 2GPI can be opsonized by anti-beta 2GPI 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-beta 2GPI (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).
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