Evidence map›Paper›PMID 28114394›Full record

ArticlePloS one2017

Proteomic Analysis of Kveim Reagent Identifies Targets of Cellular Immunity in Sarcoidosis.

Christian Eberhardt, Muhunthan Thillai, Robert Parker, Nazneen Siddiqui, Lee Potiphar, Rob Goldin, John F Timms, Athol U Wells, Onn M Kon, Melissa Wickremasinghe and 3 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
4.5field-weighted citation impact, top 5% 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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Sarcoidosis as an Autoimmune Disease.Frontiers in immunology · 2019
    Pooled it
  2. Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Inflammatory Pathways in Sarcoidosis.Advances in experimental medicine and biology · 2021
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Environmental Risk Factors for Sarcoidosis.Frontiers in immunology · 2020
    Review
  18. Observational
  19. Frontiers in immunology · 2018
    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

13 authors at 5 institutions in 1 country.

Christian EberhardtTuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Muhunthan ThillaiCambridge Interstitial Lung Disease Group, Papworth NHS Trust, Cambridge, United Kingdom.
Robert ParkerTuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Nazneen SiddiquiTuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Lee PotipharTuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Rob GoldinCentre for Pathology, Department of Medicine, Imperial College London, London, United Kingdom.
John F TimmsInstitute for Women's Health, Faculty of Population Health Sciences, University College London, London, United Kingdom.
Athol U WellsInterstitial Lung Unit, Royal Brompton Hospital, Imperial College London NHS Healthcare Trust, London, United Kingdom.
Onn M KonDepartment of Respiratory Medicine, St. Mary's Hospital London, Imperial College London NHS Healthcare Trust, London, United Kingdom.
Melissa WickremasingheDepartment of Respiratory Medicine, St. Mary's Hospital London, Imperial College London NHS Healthcare Trust, London, United Kingdom.
Donald MitchellTuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Mark E WeeksBarts Cancer Institute- a Cancer Research UK Centre of Excellence, Queen Mary University of London, John Vane Science Centre, Charterhouse Square, London EC1M 6BQ, United Kingdom.
Ajit LalvaniTuberculosis Research Unit, National Heart and Lung Institute, Imperial College London, London, United Kingdom.
Imperial College London · GBPapworth Hospital · GBQueen Mary University of London · GBSt Mary's Hospital · GBUniversity College London · GB

Funding

Medical Research Council G0801620Wellcome Trust
6 · The paper itself

Abstract

backgroundKveim-reagent (Kv) skin testing was a historical method of diagnosing sarcoidosis. Intradermal injection of treated sarcoidosis spleen tissue resulted in a granuloma response at injection site by 4-6 weeks. Previous work indicates proteins as the possible trigger of this reaction. We aimed to identify Kv-specific proteins and characterise the ex vivo response of Peripheral Blood Mononuclear Cells (PBMCs) from sarcoidosis, tuberculosis and healthy control patients when stimulated with both Kv and selected Kv-specific proteins.

methodsKv extracts were separated by 1D-SDS-PAGE and 2D-DIGE and then underwent mass spectrometric analysis for protein identification. Sarcoidosis and control PBMCs were first stimulated with Kv and then with three selected recombinant protein candidates which were identified from the proteomic analysis. PBMC secreted cytokines were subsequently measured by Multiplex Cytokine Assay.

resultsWe observed significantly increased IFN-γ and TNF-α secretion from Kv-stimulated PBMCs of sarcoidosis patients vs. PBMCs from healthy volunteers (IFN-γ: 207.2 pg/mL vs. 3.86 pg/mL, p = 0.0018; TNF-α: 2375 pg/mL vs. 42.82 pg/mL, p = 0.0003). Through proteomic approaches we then identified 74 sarcoidosis tissue-specific proteins. Of these, 3 proteins (vimentin, tubulin and alpha-actinin-4) were identified using both 1D-SDS-PAGE and 2D-DIGE. Data are available via ProteomeXchange with identifier PXD005150. Increased cytokine secretion was subsequently observed with vimentin stimulation of sarcoidosis PBMCs vs. tuberculosis PBMCs (IFN-γ: 396.6 pg/mL vs 0.1 pg/mL, p = 0.0009; TNF-α: 1139 pg/mL vs 0.1 pg/mL, p<0.0001). This finding was also observed in vimentin stimulation of sarcoidosis PBMCs compared to PBMCs from healthy controls (IFN-γ: 396.6 pg/mL vs. 0.1 pg/mL, p = 0.014; TNF-α: 1139 pg/mL vs 42.29 pg/mL, p = 0.027). No difference was found in cytokine secretion between sarcoidosis and control PBMCs when stimulated with either tubulin or alpha-actinin-4.

conclusionsStimulation with both Kveim reagent and vimentin induces a specific pro-inflammatory cytokine secretion from sarcoidosis PBMCs. Further investigation of cellular immune responses to Kveim-specific proteins may identify novel biomarkers to assist the diagnosis of sarcoidosis.

Indexed as

Immunity, CellularProteomicsAdultElectrophoresis, Polyacrylamide GelFemaleHumansIndicators and ReagentsMaleMiddle AgedSarcoidosisTandem Mass SpectrometryIndicators and Reagents

Identifiers

PMID28114394
PMCPMC5256960
OpenAlexW2581061949

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.