Evidence map›Paper›PMID 25581259›Full record

ArticleClinical and experimental immunology2015

Immunological potential of cytotoxic T lymphocyte antigen 4 immunoglobulin in murine autoimmune cholangitis.

H Tanaka, G-X Yang, T Tomiyama, K Tsuneyama, W Zhang, P S C Leung, R L Coppel, T Joh, S G Nadler, A A Ansari and 2 more

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

Article in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
1.4field-weighted citation impact, top 19% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. 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 6 institutions in 3 countries.

H TanakaDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
G-X YangDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
T TomiyamaDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
K TsuneyamaDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
W ZhangDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
P S C LeungDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
R L CoppelDepartment of Microbiology, Monash University, Melbourne, Victoria, Australia.
T JohDepartment of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
S G NadlerDepartment of Immunology, Bristol Myers Squibb, Princeton, NJ, USA.
A A AnsariDepartment of Pathology, Emory University School of Medicine, Atlanta, GA, USA.
C BowlusDivision of Gastroenterology and Hepatology, University of California at Davis School of Medicine, Sacramento, CA, USA.
M E GershwinDivision of Rheumatology, Allergy and Clinical Immunology, University of California at Davis, Davis, CA, USA.
University of California, Davis · USBristol-Myers Squibb (United States) · USEmory University · USKansai Medical University · JPMonash University · AUNagoya City University · JP

Funding

XENOBIOTICS AND PRIMARY BILIARY CIRRHOSISR01DK067003 · NIDDK · UNIVERSITY OF CALIFORNIA DAVIS · PI GERSHWIN, MERRILL E · 2003 to 2017
$4.4M
dnTGF Beta RII Mice and PBCR01DK090019 · NIDDK · UNIVERSITY OF CALIFORNIA AT DAVIS · PI GERSHWIN, MERRILL E, RIDGWAY, WILLIAM M · 2010 to 2017
$3.8M
NIDDK NIH HHS R01 DK067003NIDDK NIH HHS R01 DK090019
6 · The paper itself

Abstract

Cytotoxic T lymphocyte antigen 4 (CTLA-4) immunoglobulin (Ig) is an important regulator of T cell activation and a fusion protein directed at CD80 and CD86; it blocks co-stimulatory signalling and T cell activation. We have taken advantage of a murine model of human primary biliary cirrhosis (PBC), mice expressing a transforming growth factor (TGF)-β receptor II dominant negative (dnTGF-βRII) transgene to address the potential therapeutic efficacy of CTLA-4 Ig. To mimic patients with PBC at different stages or duration of disease, we treated mice with either CTLA-4 Ig or control IgG three times weekly from 3 to 12 or 24 weeks of age, or from 12 to 24 weeks of age. CTLA-4 Ig treatment from 3 weeks of age significantly reduced liver inflammation to 12 weeks of age. Treatment initiated at 12 weeks of age also ameliorated the autoimmune cholangitis at 24 weeks of age. However, in mice treated at 3 weeks of age, suppression of liver inflammation was not sustained and colitis was aggravated when treatment was extended to 24 weeks of age. Our data indicate that, in dnTGF-βRII mice, CTLA-4 Ig treatment has short-term beneficial effects on autoimmune cholangitis, but the effect varies according to duration of treatment and the time in which therapy was initiated. Further dissection of the events that lead to the reduction in therapeutic effectiveness of CTLA-4 Ig will be critical to determining whether such efforts can be applied to human PBC.

Indexed as

AnimalsAutoantibodiesAutoimmune DiseasesAutoimmunityCholangitisCTLA-4 AntigenDisease Models, AnimalImmunoglobulin GImmunoglobulinsLiverLymphocyte ActivationMiceMice, TransgenicMitochondriaProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaAutoantibodiesCTLA-4 AntigenImmunoglobulin GImmunoglobulinsProtein Serine-Threonine KinasesReceptors, Transforming Growth Factor betaReceptor, Transforming Growth Factor-beta Type IIautoimmunitycholangitiscolitismurine modelsprimary biliary cirrhosis

Identifiers

PMID25581259
PMCPMC4449766
OpenAlexW1522398943

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.