Antiphospholipid antibodies mediate autoimmunity against dying cells

Laura Andreoli, Micaela Fredi, Cecilia Nalli, Franco Franceschini, Pier Luigi Meroni, Angela Tincani

Research output: Contribution to journalArticle

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 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).

Original languageEnglish
Pages (from-to)302-306
Number of pages5
JournalAutoimmunity
Volume46
Issue number5
DOIs
Publication statusPublished - Aug 2013

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Keywords

  • Anti-domain antibodies
  • Antiphospholipid antibodies
  • Antiphospholipid syndrome
  • Autoantibodies
  • Beta2glycoprotein I
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Andreoli, L., Fredi, M., Nalli, C., Franceschini, F., Meroni, P. L., & Tincani, A. (2013). Antiphospholipid antibodies mediate autoimmunity against dying cells. Autoimmunity, 46(5), 302-306. https://doi.org/10.3109/08916934.2013.783025