Evidence map›Paper›PMID 28008925›Full record

ArticleNature communications2016

Biallelic JAK1 mutations in immunodeficient patient with mycobacterial infection.

Davide Eletto, Siobhan O Burns, Ivan Angulo, Vincent Plagnol, Kimberly C Gilmour, Frances Henriquez, James Curtis, Miguel Gaspar, Karolin Nowak, Vanessa Daza-Cajigal and 4 more

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

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
70citing papers in PubMed, 3 pooled it
4.3field-weighted citation impact, top 4% 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

70 citing papers in PubMed, 3 syntheses or guidelines pooled it, 113 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Review
  5. Review
  6. Review
  7. Interferon-Science (New York, N.Y.) · 2024
    Review
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review

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

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

14 authors at 6 institutions in 2 countries.

Davide ElettoDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Siobhan O BurnsUniversity College London Institute of Immunity and Transplantation, London NW3 2PF, UK.
Ivan AnguloDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Vincent PlagnolUniversity College London Genetics Institute, University College London, London WC1E 6BT, UK.ORCID 0000-0002-5597-9215
Kimberly C GilmourGreat Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
Frances HenriquezGreat Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
James CurtisDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Miguel GasparDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
Karolin NowakUniversity College London Institute of Child Health, London WC1N 1EH, UK.
Vanessa Daza-CajigalUniversity College London Institute of Immunity and Transplantation, London NW3 2PF, UK.
Dinakantha KumararatneDepartment of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
Rainer DoffingerDepartment of Clinical Biochemistry and Immunology, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK.
Adrian J ThrasherGreat Ormond Street Hospital for Children NHS Foundation Trust, London WC1N 3JH, UK.
Sergey NejentsevDepartment of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK.
University of Cambridge · GBGreat Ormond Street Hospital for Children NHS Foundation Trust · GBAddenbrooke's Hospital · GBUniversity College London · GBInstitute of Infection and Immunity · CARoyal Free London NHS Foundation Trust · GB

Funding

Wellcome Trust
6 · The paper itself

Abstract

Mutations in genes encoding components of the immune system cause primary immunodeficiencies. Here, we study a patient with recurrent atypical mycobacterial infection and early-onset metastatic bladder carcinoma. Exome sequencing identified two homozygous missense germline mutations, P733L and P832S, in the JAK1 protein that mediates signalling from multiple cytokine receptors. Cells from this patient exhibit reduced JAK1 and STAT phosphorylation following cytokine stimulations, reduced induction of expression of interferon-regulated genes and dysregulated cytokine production; which are indicative of signalling defects in multiple immune response pathways including Interferon-γ production. Reconstitution experiments in the JAK1-deficient cells demonstrate that the impaired JAK1 function is mainly attributable to the effect of the P733L mutation. Further analyses of the mutant protein reveal a phosphorylation-independent role of JAK1 in signal transduction. These findings clarify JAK1 signalling mechanisms and demonstrate a critical function of JAK1 in protection against mycobacterial infection and possibly the immunological surveillance of cancer.

Indexed as

AllelesAmino Acid SequenceBase SequenceBlood CellsChildChild, PreschoolCytokinesDisease SusceptibilityFemaleFibroblastsGene Expression RegulationHumansInterferon-alphaInterferon-gammaJanus Kinase 1MaleCytokinesInterferon-alphaInterferon-gammaJAK1 protein, humanJanus Kinase 1STAT Transcription FactorsTYK2 KinaseTYK2 protein, human

Identifiers

PMID28008925
PMCPMC5196432
OpenAlexW2567351306

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.