Evidence map›Paper›PMID 25273993›Full record

ArticleRheumatology (Oxford, England)2015

Proof-of-concept study demonstrating the pathogenicity of affinity-purified IgG antibodies directed to domain I of β2-glycoprotein I in a mouse model of anti-phospholipid antibody-induced thrombosis.

Charis Pericleous, Patricia Ruiz-Limón, Zurina Romay-Penabad, Ana Carrera Marín, Acely Garza-Garcia, Lucy Murfitt, Paul C Driscoll, David S Latchman, David A Isenberg, Ian Giles and 3 more

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

Article in Rheumatology (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
6.6field-weighted citation impact, top 3% 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

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Antibodies to Domain I βDoklady. Biochemistry and biophysics · 2023
    Article
  8. Article
  9. Review
  10. Understanding the Pathophysiology of Thrombotic APS through Animal Models.International journal of molecular sciences · 2021
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. Review
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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

13 authors at 3 institutions in 3 countries.

Charis PericleousCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Patricia Ruiz-LimónCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Zurina Romay-PenabadCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Ana Carrera MarínCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Acely Garza-GarciaCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Lucy MurfittCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Paul C DriscollCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
David S LatchmanCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
David A IsenbergCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Ian GilesCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Yiannis IoannouCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK. Centre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Anisur RahmanCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK.
Silvia S PierangeliCentre for Rheumatology Research, Division of Medicine, University College London, London, UK, Division of Rheumatology, Department of Internal Medicine, University of Texas Medical Branch, Galveston, TX, USA, Structural Biology, Medical Research Council National Institute for Medical Research and Arthritis Research UK Centre for Adolescent Rheumatology, University College London Hospital and Great Ormond Street Hospital, London, UK. c.pericleous@ucl.ac.uk.
UCL Australia · AUThe University of Texas Medical Branch at Galveston · USMedical Research Council · GB

Funding

Antiphospholipid antibodies and lupus: new molecular targets for treatmentR01AR056745 · NIAMS · UNIVERSITY OF TEXAS MED BR GALVESTON · PI BRASIER, ALLAN R., GONZALEZ, EMILIO B · 2010 to 2014
$1.6M
Arthritis Research UK 19423Medical Research Council MC_U117574559Medical Research Council U117574559NIAMS NIH HHS R01 AR056745
6 · The paper itself

Abstract

objectiveIgG aPL against domain I of β2-glycoprotein I (β2GPI) [anti-DI (aDI)] is associated with the pathogenesis of APS, an autoimmune disease defined by thrombosis and pregnancy morbidity. To date, however, no study has demonstrated direct pathogenicity of IgG aDI in vivo. In this proof-of-concept study, we designed a novel system to affinity purify polyclonal aDI aPL in order to assess its prothrombotic ability in a well-characterized mouse microcirculation model for APS.

methodsTwo polyclonal IgG fractions were isolated from serum of a patient with APS, both with high aPL activity but differing in aDI activity (aDI-rich and aDI-poor). These IgG fractions were tested for their pathogenic ability in an in vivo mouse model of thrombosis. Male CD1 mice were injected intraperitoneally with either aDI-rich or aDI-poor IgG; as a control, IgG isolated from healthy serum was used. A pinch injury was applied to the right femoral vein and thrombus dynamics and tissue factor activity in isolated tissue were evaluated.

resultsBoth aDI-rich and aDI-poor IgG retained aCL and anti-β2GPI activity, while only aDI-rich IgG displayed high aDI activity, as defined by our in-house cut-offs for positivity in each assay. aDI-rich IgG induced significantly larger thrombi in vivo compared with aDI-poor IgG (P < 0.0001). Similarly, aDI-rich IgG significantly enhanced the procoagulant activity of carotid artery endothelium and peritoneal macrophages isolated from experimental animals (P < 0.01).

conclusionThese data directly demonstrate that the ability to cause thrombosis in vivo is concentrated in the aDI fraction of aPL.

Indexed as

Disease Models, AnimalMiceAnimalsAntibodies, AntiphospholipidAntiphospholipid Syndromebeta 2-Glycoprotein IImmunoglobulin GMaleProtein Structure, TertiaryThrombosisAntibodies, Antiphospholipidbeta 2-Glycoprotein IImmunoglobulin Ganti-phospholipid antibodiesanti-phospholipid syndromedomain Imouse modelvenous thrombosisβ2-glycoprotein I

Identifiers

PMID25273993
PMCPMC4372675
OpenAlexW2113197903

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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.