Evidence map›Paper›PMID 38933274›Full record

ArticleFrontiers in immunology2024

Whole-blood culture-derived cytokine combinations for the diagnosis of tuberculosis.

Anne Ahrens Østergaard, Søren Feddersen, Mike B Barnkob, Rasmus Bank Lynggaard, Amanda Cecilie Annie Karstoft, Maria Borup, Ingrid Louise Titlestad, Torben Tranborg Jensen, Ole Hilberg, Christian Wejse and 4 more

Abstract read
In one paragraph

Article in Frontiers in immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

14 authors.

Anne Ahrens ØstergaardResearch Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Søren FeddersenDepartment of Clinical Biochemistry, Odense University Hospital, Odense, Denmark.
Mike B BarnkobDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Rasmus Bank LynggaardDepartment of Clinical Biochemistry, Odense University Hospital, Odense, Denmark.
Amanda Cecilie Annie KarstoftResearch Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Maria BorupDepartment of Respiratory Medicine, Odense University Hospital, Odense, Denmark.
Ingrid Louise TitlestadDepartment of Respiratory Medicine, Odense University Hospital, Odense, Denmark.
Torben Tranborg JensenDepartment for Pulmonary Diseases, Esbjerg Hospital, Esbjerg, Denmark.
Ole HilbergDepartment of Medicine, Vejle Hospital, Hospital Lillebælt, Vejle, Denmark.
Christian WejseDepartment of Infectious Diseases, Aarhus University Hospital, Aarhus, Denmark.
Stephanie BjerrumResearch Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Morten BlaabjergResearch Unit of Neurology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Kristian AssingDepartment of Clinical Immunology, Odense University Hospital, Odense, Denmark.
Isik Somuncu JohansenResearch Unit of Infectious Diseases, Department of Clinical Research, University of Southern Denmark, Odense, Denmark.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: The diagnosis of tuberculosis (TB) disease and TB infection (TBI) remains a challenge, and there is a need for non-invasive and blood-based methods to differentiate TB from conditions mimicking TB (CMTB), TBI, and healthy controls (HC). We aimed to determine whether combination of cytokines and established biomarkers could discriminate between 1) TB and CMTB 2) TB and TBI 3) TBI and HC. Methods: We used hemoglobin, total white blood cell count, neutrophils, monocytes, C-reactive protein, and ten Meso Scale Discovery analyzed cytokines (interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, interferon (IFN)-ɣ, and tumor necrosis factor (TNF)-α) in TruCulture whole blood tubes stimulated by lipopolysaccharides (LPS), zymosan (ZYM), anti-CD3/28 (CD3), and unstimulated (Null) to develop three index tests able to differentiate TB from CMTB and TBI, and TBI from HC. Results: In 52 persons with CMTB (n=9), TB (n=23), TBI (n=10), and HC (n=10), a combination of cytokines (LPS-IFN-ɣ, ZYM-IFN-ɣ, ZYM-TNF-α, ZYM-IL-1β, LPS-IL-4, and ZYM-IL-6) and neutrophil count could differentiate TB from CMTB with a sensitivity of 52.2% (95% CI: 30.9%-73.4%) and a specificity of 100 % (66.4%-100%). Null- IFN-ɣ, Null-IL-8, CD3-IL-6, CD3-IL-8, CD3-IL-13, and ZYM IL-1b discriminated TB from TBI with a sensitivity of 73.9% (56.5% - 91.3%) and a specificity of 100% (69.2-100). Cytokines and established biomarkers failed to differentiate TBI from HC with ≥ 98% specificity. Discussion: Selected cytokines may serve as blood-based add-on tests to detect TB in a low-endemic setting, although these results need to be validated.

Indexed as

BiomarkersBlood CultureCytokinesTuberculosisAdultAgedDiagnosis, DifferentialFemaleHumansMaleMiddle AgedMycobacterium tuberculosisSensitivity and SpecificityYoung AdultBiomarkersCytokinesconditions mimicking tuberculosiscytokinesdiagnostic testrandom forest model (RF)recursive feature elimination (RFE)tuberculosistuberculosis infectionwhole blood stimulation

Identifiers

PMID38933274
PMCPMC11199390

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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.