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Oxidation of beta 2-glycoprotein I associates with IgG antibodies to domain I in patients with antiphospholipid syndrome

Raimondo, MG; Pericleous, C; Radziszewska, A; Borghi, MO; Pierangeli, S; Meroni, PL; Giles, I; ... Ioannou, Y; + view all (2017) Oxidation of beta 2-glycoprotein I associates with IgG antibodies to domain I in patients with antiphospholipid syndrome. PLoS ONE , 12 (10) , Article e0186513. 10.1371/journal.pone.0186513. Green open access

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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.

Type: Article
Title: Oxidation of beta 2-glycoprotein I associates with IgG antibodies to domain I in patients with antiphospholipid syndrome
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0186513
Publisher version: http://doi.org/10.1371/journal.pone.0186513
Language: English
Additional information: © 2017 Raimondo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, BETA(2)-GLYCOPROTEIN I, CLASSIFICATION, PATHOGENICITY, PATHOGENESIS, CRITERIA, BINDING
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10030038
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