Evidence map›Paper›PMID 39573991›Full record

ArticleBMC infectious diseases2024

Candidate serum protein biomarkers for active pulmonary tuberculosis diagnosis in tuberculosis endemic settings.

Sosina Ayalew, Teklu Wegayehu, Biniam Wondale, Azeb Tarekegn, Bamlak Tessema, Filippos Admasu, Anne Piantadosi, Maryam Sahi, Tewodros Tariku Gebresilase, Claudia Fredolini and 1 more

Erratum issuedAbstract read
In one paragraph

Article in BMC infectious diseases, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

  1. Discovery and validation of novel plasma protein biomarkers for severe tuberculosis patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors.

Sosina AyalewArmauer Hansen Research Institute, Addis Ababa, Ethiopia. absosina2011@gmail.com.
Teklu WegayehuDepartment of Biology, College of Natural and Computational Sciences, Arba Minch University, Arba Minch, Ethiopia.
Biniam WondaleDepartment of Biology, College of Natural and Computational Sciences, Arba Minch University, Arba Minch, Ethiopia.
Azeb TarekegnArmauer Hansen Research Institute, Addis Ababa, Ethiopia.
Bamlak TessemaArmauer Hansen Research Institute, Addis Ababa, Ethiopia.
Filippos AdmasuKLATASDS-MOE, School of Statistics, East China Normal University, Shanghai, China.
Anne PiantadosiDepartment of Pathology and Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, Atlanta, GA, USA.
Maryam SahiAffinity Proteomics-Stockholm Unit, SciLifeLab, Stockholm, Sweden.
Tewodros Tariku GebresilaseArmauer Hansen Research Institute, Addis Ababa, Ethiopia.
Claudia FredoliniAffinity Proteomics-Stockholm Unit, SciLifeLab, Stockholm, Sweden.
Adane MihretArmauer Hansen Research Institute, Addis Ababa, Ethiopia.

Funding

Emory/Georgia TB Research Advancement Center (TRAC)P30AI168386 · NIAID · EMORY UNIVERSITY · PI Jeffrey M Collins · 2022 to 2026
$5.8M
Ethiopia-Emory TB Research Training ProgramD43TW009127 · FIC · EMORY UNIVERSITY · PI HENRY M BLUMBERG, Kidist Bobosha · 2013 to 2026
$3.4M
FIC NIH HHS D43 TW009127NIAID NIH HHS P30 AI168386
6 · The paper itself

Abstract

backgroundIdentification of non-sputum diagnostic markers for tuberculosis (TB) is urgently needed. This exploratory study aimed to discover potential serum protein biomarkers for the diagnosis of active pulmonary TB (PTB).

methodWe employed Proximity Extension Assay (PEA) to measure levels of 92 protein biomarkers related to inflammation in serum samples from three patient groups: 30 patients with active PTB, 29 patients with other respiratory diseases with latent TB (ORD with LTBI+), and 29 patients with other respiratory diseases without latent TB (ORD with LTBI-). To understand the functional mechanisms associated with differentially expressed proteins, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Least absolute shrinkage and selection operator (LASSO) regression was employed to identify potential TB diagnostic protein biomarkers. Network interactions among the identified candidate diagnostic markers were then analyzed, and their diagnostic performance was evaluated using logistic regression and receiver operating characteristic (ROC) analysis.

resultThe analysis revealed 37 differentially expressed proteins (DEPs) in the active PTB group compared to both ORD with LTBI + and ORD with LTBI- groups. Gene Ontology analysis indicated that these DEPs were primarily involved in the inflammatory response, while KEGG enrichment analysis highlighted the cytokine-cytokine receptor interaction pathway as the top significant hit. LASSO regression identified eight promising candidate protein biomarkers: IFN-gamma, LIF, uPA, CSF-1, SCF, SIRT2, 4E-BP1, and GDNF. The combined set of these eight proteins yielded an AUC of 0.943 for differentiating active PTB from ORD with LTBI+, and an AUC of 0.927 for distinguishing PTB from ORD with LTBI-.

conclusionWe have identified eight protein markers that reliably differentiate active PTB from ORD irrespective of LTBI presence. Further large-scale validation and translation of these protein markers into a user-friendly and affordable point-of-care test hold the potential to significantly enhance TB control in high-burden regions.

Indexed as

BiomarkersBlood ProteinsTuberculosis, PulmonaryAdultFemaleHumansLatent TuberculosisMaleMiddle AgedROC CurveBiomarkersBlood ProteinsProximity extension assaySerum protein markersTuberculosis diagnosis

Identifiers

PMID39573991
PMCPMC11583743

What Socratic holds

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LicenceCC BY-NC-ND
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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 Socratic graph.