Evidence map›Paper›PMID 24848066›Full record

ArticleDiabetes2014

Nardilysin-dependent proteolysis of cell-associated VTCN1 (B7-H4) marks type 1 diabetes development.

Ilian A Radichev, Lilia V Maneva-Radicheva, Christina Amatya, Camille Parker, Jacob Ellefson, Clive Wasserfall, Mark Atkinson, Paul Burn, Alexei Y Savinov

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Diabetes, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
–field-weighted citation impact
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

19 citing papers in PubMed.

  1. Article
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  11. Article
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  14. New B7 Family Checkpoints in Human Cancers.Molecular cancer therapeutics · 2017
    Review
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  17. Article
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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

9 authors.

Ilian A RadichevSanford Project/Children's Health Research Center at Sanford Research, Sioux Falls, SD Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD.
Lilia V Maneva-RadichevaSanford Project/Children's Health Research Center at Sanford Research, Sioux Falls, SD Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD.
Christina AmatyaSanford Project/Children's Health Research Center at Sanford Research, Sioux Falls, SD Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD.
Camille ParkerSanford Project/Children's Health Research Center at Sanford Research, Sioux Falls, SD Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD.
Jacob EllefsonSanford Project/Children's Health Research Center at Sanford Research, Sioux Falls, SD Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD.
Clive WasserfallDepartment of Pathology, College of Medicine, University of Florida, Gainesville, FL.
Mark AtkinsonDepartment of Pathology, College of Medicine, University of Florida, Gainesville, FL.
Paul BurnSanford Project/Children's Health Research Center at Sanford Research, Sioux Falls, SD Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD.
Alexei Y SavinovSanford Project/Children's Health Research Center at Sanford Research, Sioux Falls, SD Department of Pediatrics, University of South Dakota School of Medicine, Sioux Falls, SD alexei.savinov@sanfordhealth.org.

Funding

CENTER FOR CANCER BIOLOGY RESEARCHP20RR024219 · NCRR · SANFORD RESEARCH/USD · PI MISKIMINS, W KEITH · 2011 to 2011
$2.3M
NCRR NIH HHS 1P20RR024219NCRR NIH HHS P20 RR024219
6 · The paper itself

Abstract

T-cell responses directed against insulin-secreting pancreatic β-cells are the key events highlighting type 1 diabetes (T1D). Therefore, a defective control of T-cell activation is thought to underlie T1D development. Recent studies implicated a B7-like negative costimulatory protein, V-set domain-containing T-cell activation inhibitor-1 (VTCN1), as a molecule capable of inhibiting T-cell activation and, potentially, an important constituent in experimental models of T1D. Here, we unravel a general deficiency within the VTCN1 pathway that is shared between diabetes-prone mice and a subset of T1D patients. Gradual loss of membrane-tethered VTCN1 from antigen-presenting cells combined with an increased release of soluble VTCN1 (sVTCN1) occurs in parallel to natural T1D development, potentiating hyperproliferation of diabetogenic T cells. Mechanistically, we demonstrate that the loss of membrane-tethered VTCN1 is linked to proteolytic cleavage mediated by the metalloproteinase nardilysin. The cleaved sVTCN1 fragment was detected at high levels in the peripheral blood of 53% T1D patients compared with only 9% of the healthy subjects. Elevated blood sVTCN1 levels appeared early in the disease progression and correlated with the aggressive pace of disease, highlighting the potential use of sVTCN1 as a new T1D biomarker, and identifying nardilysin as a potential therapeutic target.

Indexed as

AdolescentAdultAnimalsBiomarkersChildDiabetes Mellitus, Type 1Disease ProgressionFemaleHumansMaleMetalloendopeptidasesMiceMice, Inbred NODSignal TransductionT-LymphocytesV-Set Domain-Containing T-Cell Activation Inhibitor 1BiomarkersMetalloendopeptidasesnardilysinV-Set Domain-Containing T-Cell Activation Inhibitor 1VTCN1 protein, human

Identifiers

PMID24848066
PMCPMC4171653

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.