Evidence map›Paper›PMID 27137491›Full record

Trial reportEMBO molecular medicine2016

Inhibition of DPP4 activity in humans establishes its in vivo role in CXCL10 post-translational modification: prospective placebo-controlled clinical studies.

Jérémie Decalf, Kristin V Tarbell, Armanda Casrouge, Jeffrey D Price, Grace Linder, Estelle Mottez, Philippe Sultanik, Vincent Mallet, Stanislas Pol, Darragh Duffy and 1 more

Open access · goldAbstract readClinical Trial
In one paragraph

Trial report in EMBO molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

36 citing papers in PubMed, 47 citations in OpenAlex.

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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

11 authors at 4 institutions in 2 countries.

Jérémie DecalfThe Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France INSERM U818, Paris, France.
Kristin V TarbellDiabetes Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Armanda CasrougeThe Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France INSERM U818, Paris, France.
Jeffrey D PriceDiabetes Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Grace LinderDiabetes Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
Estelle MottezCenter for Human Immunology, Institut Pasteur, Paris, France.
Philippe SultanikDépartement d'Hépatologie, AP-HP, Hôpital Cochin, Université Paris Descartes, INSERM UMS20, Institut Pasteur, Paris, France.
Vincent MalletDépartement d'Hépatologie, AP-HP, Hôpital Cochin, Université Paris Descartes, INSERM UMS20, Institut Pasteur, Paris, France.
Stanislas PolDépartement d'Hépatologie, AP-HP, Hôpital Cochin, Université Paris Descartes, INSERM UMS20, Institut Pasteur, Paris, France.
Darragh DuffyThe Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France INSERM U818, Paris, France Center for Human Immunology, Institut Pasteur, Paris, France darragh.duffy@pasteur.fr albertm@pasteur.fr.ORCID 0000-0002-8875-2308
Matthew L AlbertThe Laboratory of Dendritic Cell Immunobiology, Institut Pasteur, Paris, France INSERM U818, Paris, France Center for Human Immunology, Institut Pasteur, Paris, France Department of Cancer Immunotherapy, Genentech, South San Francisco, CA, USA darragh.duffy@pasteur.fr albertm@pasteur.fr.
Inserm · FRDélégation Paris 5 · FRNational Institutes of Health · USInstitut Pasteur · FR

Funding

testing the effect of a DPP-4 inhibitor on immune functionZIADK075019 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI TARBELL, KRISTIN · 2009 to 2017
$2.2M
6 · The paper itself

Abstract

Biochemical experiments, animal models, and observational studies in humans all support a role of dipeptidyl peptidase 4 (DPP4) in the N-terminal truncation of CXCL10, which results in the generation of an antagonist form of the chemokine that limits T-cell and NK cell migration. Motivated by the ability to regulate lymphocyte trafficking in vivo, we conducted two prospective clinical trials to test the effects of DPP4 inhibition on CXCL10 processing in healthy donors and in chronic hepatitis C patients, a disease in which DPP4 levels are found to be elevated. Participants were treated daily with 100 mg sitagliptin, a clinically approved DPP4 inhibitor. Plasma samples were analyzed using an ultrasensitive single-molecule assay (Simoa) to distinguish the full-length CXCL101-77 from the NH2-truncated CXCL103-77, as compared to the total CXCL10 levels. Sitagliptin treatment resulted in a significant decrease in CXCL103-77 concentration, a reciprocal increase in CXCL101-77, with only minimal effects on total levels of the chemokine. These data provide the first direct evidence that in vivo DPP4 inhibition in humans can preserve the bioactive form of CXCL10, offering new therapeutic opportunities for DPP4 inhibitors.

Indexed as

Protein Processing, Post-TranslationalChemokine CXCL10Dipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsHealthy VolunteersHepatitis C, ChronicHumansPlacebosProspective StudiesProteolysisSitagliptin PhosphateChemokine CXCL10CXCL10 protein, humanDipeptidyl Peptidase 4Dipeptidyl-Peptidase IV InhibitorsDPP4 protein, humanPlacebosSitagliptin Phosphatechemokinesclinical studyCXCL10DPP4post‐translational modifications

Identifiers

PMID27137491
PMCPMC4888857
OpenAlexW2327058228

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.