Evidence map›Paper›PMID 25405480›Full record

ArticlePloS one2014

Assessment of CD4+ T cell responses to glutamic acid decarboxylase 65 using DQ8 tetramers reveals a pathogenic role of GAD65 121-140 and GAD65 250-266 in T1D development.

I-Ting Chow, Junbao Yang, Theresa J Gates, Eddie A James, Duy T Mai, Carla Greenbaum, William W Kwok

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 39 citations in OpenAlex.

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  16. Regulatory CD4Circulation · 2018
    Article
  17. Article
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  19. Review
  20. Autoreactive T cells in type 1 diabetes.The Journal of clinical investigation · 2017
    Review
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

7 authors at 2 institutions in 1 country.

I-Ting ChowBenaroya Research Institute at Virginia Mason, Seattle, WA, United States of America.
Junbao YangBenaroya Research Institute at Virginia Mason, Seattle, WA, United States of America.
Theresa J GatesBenaroya Research Institute at Virginia Mason, Seattle, WA, United States of America.
Eddie A JamesBenaroya Research Institute at Virginia Mason, Seattle, WA, United States of America.
Duy T MaiBenaroya Research Institute at Virginia Mason, Seattle, WA, United States of America.
Carla GreenbaumBenaroya Research Institute at Virginia Mason, Seattle, WA, United States of America.
William W KwokBenaroya Research Institute at Virginia Mason, Seattle, WA, United States of America; Department of Medicine, University of Washington, Seattle, WA, United States of America.
Virginia Mason Medical Center · USBenaroya Research Institute

Funding

Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · PI Karin E Bornfeldt · 1986 to 2026
$41.4M
Mechanisms for HLA-DQ mediated disease protection and susceptibilityDP3DK097653 · NIDDK · BENAROYA RESEARCH INST AT VIRGINIA MASON · PI KWOK, WILLIAM W. · 2012 to 2012
$3.5M
NIDDK NIH HHS DP3 DK097653NIDDK NIH HHS P30 DK017047
6 · The paper itself

Abstract

Susceptibility to type 1 diabetes (T1D) is strongly associated with MHC class II molecules, particularly HLA-DQ8 (DQ8: DQA1*03:01/DQB1*03:02). Monitoring T1D-specific T cell responses to DQ8-restricted epitopes may be key to understanding the immunopathology of the disease. In this study, we examined DQ8-restricted T cell responses to glutamic acid decarboxylase 65 (GAD65) using DQ8 tetramers. We demonstrated that GAD65 121-140 and GAD65 250-266 elicited responses from DQ8+ subjects. Circulating CD4+ T cells specific for these epitopes were detected significantly more often in T1D patients than in healthy individuals after in vitro expansion. T cell clones specific for GAD65 121-140 and GAD65 250-266 carried a Th1-dominant phenotype, with some of the GAD65 121-140-specific T cell clones producing IL-17. GAD65 250-266-specific CD4+ T cells could also be detected by direct ex vivo staining. Analysis of unmanipulated peripheral blood mononuclear cells (PBMCs) revealed that GAD65 250-266-specific T cells could be found in both healthy and diabetic individuals but the frequencies of specific T cells were higher in subjects with type 1 diabetes. Taken together, our results suggest a proinflammatory role for T cells specific for DQ8-restricted GAD65 121-140 and GAD65 250-266 epitopes and implicate their possible contribution to the progression of T1D.

Indexed as

CD4-Positive T-LymphocytesDiabetes Mellitus, Type 1Glutamate DecarboxylaseHLA-DQ AntigensHumansStatistics, NonparametricWashingtonGlutamate DecarboxylaseHLA-DQ8 antigenHLA-DQ Antigens

Identifiers

PMID25405480
PMCPMC4236121
OpenAlexW2085116014

What OpenQuestion holds

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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.