Evidence map›Paper›PMID 30124466›Full record

ArticleThe Journal of clinical investigation2018

The endothelial cell receptor stabilin-2 regulates VWF-FVIII complex half-life and immunogenicity.

Laura L Swystun, Jesse D Lai, Colleen Notley, Ilinca Georgescu, A Simonne Paine, Jeff Mewburn, Kate Nesbitt, Kai Schledzewski, Cyrill Géraud, Julia Kzhyshkowska and 5 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed, 1 pooled it
6.5field-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

49 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
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  5. Review
  6. Article
  7. Large deletions in theResearch and practice in thrombosis and haemostasis · 2025
    Article
  8. Article
  9. Article
  10. Rare variants inERJ open research · 2025
    Article
  11. Article
  12. Identification of multiple novel procoagulant plasma ligands for stabilin-2.Journal of thrombosis and haemostasis : JTH · 2025
    Article
  13. Venous thromboembolic disease genetics: from variants to function.Journal of thrombosis and haemostasis : JTH · 2024
    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

15 authors at 4 institutions in 3 countries.

Laura L SwystunDepartment of Pathology and Molecular Medicine and.
Jesse D LaiDepartment of Pathology and Molecular Medicine and.
Colleen NotleyDepartment of Pathology and Molecular Medicine and.
Ilinca GeorgescuDepartment of Pathology and Molecular Medicine and.
A Simonne PaineDepartment of Pathology and Molecular Medicine and.
Jeff MewburnDivision of Cancer Biology and Genetics, Queen's University, Kingston, Ontario, Canada.
Kate NesbittDepartment of Pathology and Molecular Medicine and.
Kai SchledzewskiDepartment of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Cyrill GéraudDepartment of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Julia KzhyshkowskaDepartment of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Sergij GoerdtDepartment of Dermatology, Venereology and Allergology, University Medical Center and Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
Wilma HopmanDepartment of Public Health Sciences, Queen's University, Kingston, Ontario, Canada.
Robert R MontgomeryDepartment of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
Paula D JamesDepartment of Medicine, Queen's University, Kingston, Ontario, Canada.
David LillicrapDepartment of Pathology and Molecular Medicine and.
Queen's University · CAUniversity Hospital Heidelberg · DEMedical College of Wisconsin · USUniversity Medical Centre Mannheim · DE

Funding

Zimmerman Program for the Molecular and Clinical Biology of VWDP01HL081588 · NHLBI · VERSITI WISCONSIN, INC. · PI MONTGOMERY, ROBERT R · 2005 to 2016
$19.3M
Zimmerman Program on the Biology of VWDP01HL144457 · NHLBI · VERSITI WISCONSIN, INC. · PI MONTGOMERY, ROBERT R · 2019 to 2023
$13.3M
Molecular Interactions of FVIII and VWFR01HL139847 · NHLBI · VERSITI WISCONSIN, INC. · PI MONTGOMERY, ROBERT R · 2018 to 2021
$2.3M
CIHR MOP-97849NHLBI NIH HHS P01 HL081588NHLBI NIH HHS P01 HL144457NHLBI NIH HHS R01 HL139847
6 · The paper itself

Abstract

Quantitative abnormalities of the von Willebrand factor-factor VIII (VWF-FVIII) complex associate with inherited bleeding or thrombotic disorders. Receptor-mediated interactions between plasma VWF-FVIII and phagocytic or immune cells can influence their hemostatic and immunogenic activities. Genetic association studies have demonstrated that variants in the STAB2 gene, which encodes the scavenger receptor stabilin-2, associate with plasma levels of VWF-FVIII. However, the mechanistic basis and pathophysiological consequences of this association are unknown. We have demonstrated that stabilin-2-expressing cells bind and internalize human VWF and FVIII in a VWF-dependent manner, and stabilin-2-deficient mice displayed prolonged human VWF-FVIII half-life compared with controls. The stabilin-2 variant p.E2377K significantly decreased stabilin-2 expression and impaired VWF endocytosis in a heterologous expression system, and common STAB2 variants associated with plasma VWF levels in type 1 von Willebrand disease patients. STAB2-deficient mice displayed a decreased immunogenic response to human VWF-FVIII complex, while coinfusion of human VWF-FVIII with the stabilin-2 ligand hyaluronic acid attenuated the immune response to exogenous FVIII. Collectively, these data suggest that stabilin-2 functions as both a clearance and an immunoregulatory receptor for VWF-FVIII, making stabilin-2 a novel molecular target for modification of the half-life of VWF-FVIII and the immune response to VWF-FVIII concentrates.

Indexed as

AdolescentAdultAgedAnimalsCell Adhesion Molecules, NeuronalChildChild, PreschoolDrug CombinationsEndocytosisEndothelial CellsFactor VIIIFemaleGenetic VariationHalf-LifeHumansInfantCell Adhesion Molecules, NeuronalDrug CombinationsFactor VIIIfactor VIII, von Willebrand factor drug combinationSTAB2 protein, humanStab2 protein, mousevon Willebrand FactorCoagulationendothelial cellsGeneticsHematology

Identifiers

PMID30124466
PMCPMC6118640
OpenAlexW2886206473

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.