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Oxidation of β2-glycoprotein I associates with IgG antibodies to domain I in patients with antiphospholipid syndrome.

Authors
  • Raimondo, Maria Gabriella1, 2
  • Pericleous, Charis1
  • Radziszewska, Anna1, 3
  • Borghi, Maria Orietta2, 4
  • Pierangeli, Silvia5
  • Meroni, Pier Luigi2, 4
  • Giles, Ian1
  • Rahman, Anisur1
  • Ioannou, Yiannis1, 3
  • 1 Centre for Rheumatology Research, UCL Division of Medicine, London, United Kingdom. , (United Kingdom)
  • 2 Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy. , (Italy)
  • 3 Arthritis Research UK Centre for Adolescent Rheumatology, UCL Division of Medicine, London, United Kingdom. , (United Kingdom)
  • 4 IRCCS Istituto Auxologico Italiano, Milan, Italy. , (Italy)
  • 5 Division of Rheumatology, Department of Medicine, University of Texas Medical Branch, Galveston, Texas.
Type
Published Article
Journal
PLoS ONE
Publisher
Public Library of Science
Publication Date
Jan 01, 2017
Volume
12
Issue
10
Identifiers
DOI: 10.1371/journal.pone.0186513
PMID: 29049363
Source
Medline
Language
English
License
Unknown

Abstract

Domain I (DI) of beta-2-glycoprotein I (β2GPI) contains the immunodominant epitope for pathogenic antiphospholipid antibodies (aPL). DI is exposed in the linear form of the molecule but not in the circular form that comprises 90% of serum β2GPI. The majority of circulating β2GPI is biochemically reduced with two free thiols in Domain V. However, increased levels of oxidised β2GPI are found in patients with antiphospholipid syndrome (APS). It is not known whether oxidation of β2GPI favours the linear form of the molecule and thus promotes development of anti-DI antibodies. We investigated whether the proportion of oxidised β2GPI associates with the presence of anti-DI in APS patients. Serum samples from 44 APS patients were screened for IgG, IgM and IgA anti-DI, anti-β2GPI, anti-cardiolipin (anti-CL) and biochemically reduced β2GPI. A negative correlation was found between the proportion of β2GPI in the biochemically reduced form and IgG anti-DI levels (r = -0.54, p = 0.0002), but not with IgM or IgA anti-DI. Moreover, the proportion of β2GPI in the reduced form was lower in IgG anti-DI positive than anti-DI negative APS patients (p = 0.02). The relative amount of reduced β2GPI was no different between patients who were positive or negative for IgG, IgM and IgA anti-β2GPI or anti-CL. This study demonstrates that oxidised β2GPI lacking free cysteine-thiol groups most closely associates with IgG anti-DI positivity compared to IgG anti-CL and anti-β2GPI. Future studies are required to ascertain the directionality of this association to define causation.

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