UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Antibodies to FXa and thrombin in patients with SLE differentially regulate C3 and C5 cleavage

McDonnell, Thomas; Amarnani, Raj; Spicer, Carina; Jbari, Hajar; Pericleous, Charis; Spiteri, Valentina A; Wincup, Chris; ... Giles, Ian; + view all (2022) Antibodies to FXa and thrombin in patients with SLE differentially regulate C3 and C5 cleavage. Lupus Science & Medicine , 9 (1) , Article e000738. 10.1136/lupus-2022-000738. Green open access

[thumbnail of e000738.full.pdf]
Preview
PDF
e000738.full.pdf - Published Version

Download (1MB) | Preview

Abstract

OBJECTIVES: The significance of antibodies directed against activated factor X (FXa) and thrombin (Thr) in patients with SLE and/or antiphospholipid syndrome (APS) is unknown. FXa and Thr are coregulated by antithrombin (AT) and activate complement. Therefore, we studied the ability of anti activated factor X (aFXa) and/or anti-(a)Thr IgG from patients with SLE±APS to modulate complement activation. METHODS: Patients with SLE±APS were selected on the basis of known aThr and/or aFXa IgG positivity, and the effects of affinity-purified aFXa/aThr IgG on FXa and Thr-mediated C3 and C5 activation were measured ±AT. Structural analyses of FXa and Thr and AT-FXa and AT-Thr complexes were analysed in conjunction with the in vitro ability of AT to regulate aFXa-FXa and aThr-Thr-mediated C3/C5 activation. RESULTS: Using affinity-purified IgG from n=14 patients, we found that aThr IgG increased Thr-mediated activation of C3 and C5, while aFXa IgG did not increase C3 or C5 activation. Structural analysis identified potential epitopes and predicted a higher likelihood of steric hindrance of AT on FXa by aFXa IgG compared with the AT-Thr-aThr IgG complex that was confirmed by in vitro studies. Longitudinal analysis of 58 patients with SLE (±APS) did not find a significant association between positivity for aFXa or aTHr IgG and C3 levels or disease activity, although there was a trend for patients positive for aFXa IgG alone or both aFXa and aThr IgG to have lower levels of C3 compared with aThr IgG alone during clinical visits. CONCLUSIONS: We propose a novel method of complement regulation in patients with SLE±APS whereby aFXa and aThr IgG may have differential effects on complement activation.

Type: Article
Title: Antibodies to FXa and thrombin in patients with SLE differentially regulate C3 and C5 cleavage
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1136/lupus-2022-000738
Publisher version: http://dx.doi.org/10.1136/lupus-2022-000738
Language: English
Additional information: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.
Keywords: Antibodies, Antiphospholipid, Autoantibodies, Systemic Lupus Erythematosus
UCL classification: 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 > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
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 > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
UCL > Provost and Vice Provost Offices > UCL BEAMS
URI: https://discovery.ucl.ac.uk/id/eprint/10154699
Downloads since deposit
19Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item