Evidence map›Paper›PMID 24561305›Full record

ArticleDiabetes2014

A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes.

Ricardo C Ferreira, Hui Guo, Richard M R Coulson, Deborah J Smyth, Marcin L Pekalski, Oliver S Burren, Antony J Cutler, James D Doecke, Shaun Flint, Eoin F McKinney and 11 more

Open access · bronzeAbstract 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 213 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
213citing papers in PubMed, 2 pooled it
21.2field-weighted citation impact, top 1% 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

213 citing papers in PubMed, 2 syntheses or guidelines pooled it, 315 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
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  6. Article
  7. ProtectiveiScience · 2026
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  17. Bone marrow-derived CD169Experimental & molecular medicine · 2025
    Article
  18. Article
  19. Review
  20. Review

153 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 5 institutions in 2 countries.

Ricardo C FerreiraJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
Hui GuoJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
Richard M R CoulsonJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, U.K.
Deborah J SmythJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
Marcin L PekalskiJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
Oliver S BurrenJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
Antony J CutlerJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
James D DoeckeJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.The Australian E-Health Research Centre, Royal Brisbane and Women's Hospital, Queensland, AustraliaThe Commonwealth Scientific and Industrial Research Organisation (CSIRO) Preventative Health Flagship, Victoria, AustraliaCSIRO Mathematics and Information Sciences, Macquarie University, New South Wales, Australia.
Shaun FlintCambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, U.K.
Eoin F McKinneyCambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, U.K.
Paul A LyonsCambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, U.K.
Kenneth G C SmithCambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge, U.K.
Peter AchenbachInstitute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, München, Germany.
Andreas BeyerleinInstitute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, München, Germany.
David B DungerDepartment of Paediatrics, School of Clinical Medicine, University of Cambridge, Cambridge, U.K.
David G ClaytonJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
Linda S WickerJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K.
John A ToddJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K. john.todd@cimr.cam.ac.uk chris.wallace@cimr.cam.ac.uk anette-g.ziegler@helmholtz-muenchen.de.
Ezio BonifacioCRTD-DFG Research Center for Regenerative Therapies Dresden and Paul Langerhans Institute Dresden, Technische Universität Dresden, Dresden, Germany.
Chris WallaceJDRF/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, NIHR Cambridge Biomedical Research Centre, Cambridge Institute for Medical Research, University of Cambridge, Cambridge, U.K. john.todd@cimr.cam.ac.uk chris.wallace@cimr.cam.ac.uk anette-g.ziegler@helmholtz-muenchen.de.
Anette-G ZieglerInstitute of Diabetes Research, Helmholtz Zentrum München, Neuherberg, and Forschergruppe Diabetes, Klinikum rechts der Isar, Technische Universität München, München, Germany john.todd@cimr.cam.ac.uk chris.wallace@cimr.cam.ac.uk anette-g.ziegler@helmholtz-muenchen.de.
Commonwealth Scientific and Industrial Research Organisation · AUHelmholtz Zentrum München · DEKlinikum rechts der Isar · DEPaul Langerhans Institute Dresden · DETechnical University of Munich · DE

Funding

Medical Research Council G0600717Wellcome Trust 083650/Z/07/ZWellcome Trust 089989Wellcome Trust 091157Wellcome Trust 100140Wellcome Trust WT061858/091157
6 · The paper itself

Abstract

Diagnosis of the autoimmune disease type 1 diabetes (T1D) is preceded by the appearance of circulating autoantibodies to pancreatic islets. However, almost nothing is known about events leading to this islet autoimmunity. Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D. Here, we first used DNA microarray analysis to identify IFN-β-inducible genes in vitro and then used this set of genes to define an IFN-inducible transcriptional signature in peripheral blood mononuclear cells from a group of active systemic lupus erythematosus patients (n = 25). Using this predefined set of 225 IFN signature genes, we investigated the expression of the signature in cohorts of healthy controls (n = 87), patients with T1D (n = 64), and a large longitudinal birth cohort of children genetically predisposed to T1D (n = 109; 454 microarrayed samples). Expression of the IFN signature was increased in genetically predisposed children before the development of autoantibodies (P = 0.0012) but not in patients with established T1D. Upregulation of IFN-inducible genes was transient, temporally associated with a recent history of upper respiratory tract infections (P = 0.0064), and marked by increased expression of SIGLEC-1 (CD169), a lectin-like receptor expressed on CD14(+) monocytes. DNA variation in IFN-inducible genes altered T1D risk (P = 0.007), as exemplified by IFIH1, one of the genes in our IFN signature for which increased expression is a known risk factor for disease. These findings identify transient increased expression of type I IFN genes in preclinical diabetes as a risk factor for autoimmunity in children with a genetic predisposition to T1D.

Indexed as

AdolescentAdultAutoimmunityChildCohort StudiesDiabetes Mellitus, Type 1FemaleGene Expression RegulationGenetic Predisposition to DiseaseHumansInterferon Type IMaleMiddle AgedRiskTranscriptomeYoung AdultInterferon Type I

Identifiers

PMID24561305
PMCPMC4066333
OpenAlexW2127371447

What OpenQuestion holds

Textmetadata
LicenceTDM
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.