Evidence map›Paper›PMID 36007979›Full record

ArticleLupus science & medicine2022

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

Thomas McDonnell, Raj Amarnani, Carina Spicer, Hajar Jbari, Charis Pericleous, Valentina A Spiteri, Chris Wincup, Bahar Artim-Esen, Ian Mackie, Marina Botto and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Lupus science & medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.3field-weighted citation impact, top 39% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 3 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 7 institutions in 3 countries.

Thomas McDonnellBiochemical Engineering Department, UCL, London, UK thomas.mcdonnell.11@ucl.ac.uk.ORCID 0000-0002-1712-9957
Raj AmarnaniDepartment of Rheumatology, University College London, London, UK.
Carina SpicerMerck & Co, Kenilworth, New Jersey, USA.
Hajar JbariDepartment of Rheumatology, University College London, London, UK.
Charis PericleousNational Heart and Lung Institute, Imperial College London, London, UK.
Valentina A SpiteriDepartment of Structural and Molecular Biology, University College London, London, UK.
Chris WincupDepartment of Rheumatology, University College London, London, UK.ORCID 0000-0002-8742-8311
Bahar Artim-EsenDepartment of Internal Medicine, Istanbul University, Fatih, Turkey.
Ian MackieDepartment of Haematology, University College London, London, UK.
Marina BottoNational Heart and Lung Institute, Imperial College London, London, UK.
Anisur RahmanDepartment of Rheumatology, University College London, London, UK.ORCID 0000-0003-2346-4484
Ian GilesDepartment of Rheumatology, University College London, London, UK.
University College London · GBBiochemical Society · GBFatih University · TRImperial College Healthcare NHS Trust · GBImperial College London · GBInstitute of Structural and Molecular Biology · GBMerck & Co., Inc., Rahway, NJ, USA (United States) · US

Funding

Medical Research Council MR/P017371/1MRF_ MRF-057-0004-RG-MCDO-C0800Versus Arthritis 21223Versus Arthritis 21992
6 · The paper itself

Abstract

objectivesThe 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.

methodsPatients 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.

resultsUsing 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.

conclusionsWe propose a novel method of complement regulation in patients with SLE±APS whereby aFXa and aThr IgG may have differential effects on complement activation.

Indexed as

Antiphospholipid SyndromeLupus Erythematosus, SystemicComplement System ProteinsFactor XHumansImmunoglobulin GThrombinComplement System ProteinsFactor XImmunoglobulin GThrombinAntibodies, AntiphospholipidAutoantibodiesSystemic Lupus Erythematosus

Identifiers

PMID36007979
PMCPMC9422842
OpenAlexW4293239166

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.