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.
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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 > 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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