Post-translational modifications of proteins in antiphospholipid antibody syndrome

Brigitta Buttari, Elisabetta Profumo, Antonella Capozzi, Luciano Saso, Maurizio Sorice, Rachele Riganò

Research output: Contribution to journalReview articlepeer-review

Abstract

Antiphospholipid antibody syndrome (APS) is a systemic autoimmune disease characterized by arterial and venous thrombosis and/or pregnancy morbidity. The incidence is around five new cases/100,000 persons per year and the prevalence is around 40–50 cases/100,000. The prevalence is higher (about 30%) among patients with systemic lupus erythematosus. APS is associated with circulating antiphospholipid antibodies (aPLs), a heterogeneous group of autoantibodies directed against negatively charged molecules and a combination of protein-complexed phospholipids. The predominant protein antigen in this disorder is beta 2-glycoprotein I (β2GPI). Despite the discovery of “new” antigenic targets and development of “new” methodological approaches, the laboratory diagnosis of APS is still an evolving field and studies to identify further antigenic target(s) as potential diagnostic markers and risk predictors are in progress. In particular, recent studies were aimed at analyzing the pathogenic role of post-translational modifications (PTMs) of proteins induced by inflammation and/or oxidative stress as modulators of protein structure and function and possibly as a source of antigenic epitopes. The present review is focused on PTMs of self-proteins responsible for autoimmune reactions in patients with APS. At present, the known PTMs in APS involve β2GPI. In particular, the PTM of β2GPI via thiol-exchange reactions is a highly specific phenomenon that makes the protein more antigenic. Other PTMs, including sialylation and acetylation, may affect β2GPI antigenicity. Moreover, the addition or loss of carbohydrate chains affects β2GPI immunoreactivity since carbohydrates are determining factors for β2GPI conformation. In addition to β2GPI, PTMs of other self proteins such as vimentin and annexins may play a role in the immune response during APS. The study of PTMs is useful to clarify the role of modified proteins in the pathogenesis of APS as well as to design more efficient diagnostic/prognostic tools and more targeted therapeutic approaches.

Original languageEnglish
Pages (from-to)511-525
Number of pages15
JournalCritical Reviews in Clinical Laboratory Sciences
Volume56
Issue number8
DOIs
Publication statusPublished - Nov 17 2019

Keywords

  • Antiphospholipid antibody syndrome
  • inflammation
  • oxidative stress
  • post-translational modification
  • β2-glycoprotein I

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Clinical Biochemistry
  • Biochemistry, medical

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