Evidence map›Paper›PMID 36454773›Full record

ArticlePloS one2022

Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis.

Stuart Meier, James A Seddon, Elizna Maasdorp, Léanie Kleynhans, Nelita du Plessis, Andre G Loxton, Stephanus T Malherbe, Daniel E Zak, Ethan Thompson, Fergal J Duffy and 11 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
1.2field-weighted citation impact, top 22% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. NETosis in hypersensitivity disorders.Molecular biology reports · 2025
    Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. International journal of molecular sciences · 2023
    Review
  12. Neutrophils inVaccines · 2023
    Review
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

21 authors at 8 institutions in 6 countries.

Stuart MeierDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
James A SeddonSouth African Tuberculosis Bioinformatics Initiative, Stellenbosch University, Cape Town, South Africa.
Elizna MaasdorpDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
Léanie KleynhansDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
Nelita du PlessisDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
Andre G LoxtonDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
Stephanus T MalherbeDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
Daniel E ZakSeattle Children's Research Institute, Center for Global Infectious Disease Research, Seattle, WA, United States of America.
Ethan ThompsonSeattle Children's Research Institute, Center for Global Infectious Disease Research, Seattle, WA, United States of America.
Fergal J DuffySeattle Children's Research Institute, Center for Global Infectious Disease Research, Seattle, WA, United States of America.
Stefan H E KaufmannMax Planck Institute for Infection Biology, Berlin, Germany.
Tom H M OttenhoffDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
Thomas J ScribaSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.
Sara SulimanSouth African Tuberculosis Vaccine Initiative, Institute of Infectious Disease and Molecular Medicine and Division of Immunology, Department of Pathology, University of Cape Town, Cape Town, South Africa.ORCID 0000-0002-5154-576X
Jayne S SutherlandVaccines & Immunity Theme, Medical Research Council Unit, The Gambia, at the London School of Hygiene and Tropical Medicine, Banjul, The Gambia.
Jill WinterCatalysis Foundation for Health, San Ramon, CA, United States of America.
Helena KuivaniemiDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0001-5753-8766
Gerhard WalzlDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.
Gerard TrompDivision of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa.ORCID 0000-0002-7761-0806
GC6-74 Consortium
Catalysis TB Biomarkers Consortium
South African Medical Research Council · ZAInfectious Disease Research Institute · USUniversity of Cape Town · ZACatalysis Foundation for Health · USDesmond Tutu HIV Foundation · ZAInstitute for Advanced Study · USLeiden University Medical Center · NLMRC Unit the Gambia · GM

Funding

Medical Research Council MC_U190071468Medical Research Council MC_UP_A900_1122Medical Research Council MC_UU_00031/6Medical Research Council MR/R007942/1
6 · The paper itself

Abstract

Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease. We analyzed longitudinal RNA sequencing (RNAseq) data from the whole blood of 74 TB progressors whose samples were grouped into four six-month intervals preceding diagnosis (the GC6-74 study). We additionally analyzed RNAseq data from an independent cohort of 90 TB patients with positron emission tomography-computed tomography (PET-CT) scan results which were used to categorize them into groups with high and low levels of lung damage (the Catalysis TB Biomarker study). These groups were compared to non-TB controls to obtain a complete whole blood transcriptional profile for individuals spanning from early stages of M.tb infection to TB diagnosis. The results revealed a steady increase in the number of genes that were differentially expressed in progressors at time points closer to diagnosis with 278 genes at 13-18 months, 742 at 7-12 months and 5,131 detected 1-6 months before diagnosis and 9,205 detected in TB patients. A total of 2,144 differentially expressed genes were detected when comparing TB patients with high and low levels of lung damage. There was a large overlap in the genes upregulated in progressors 1-6 months before diagnosis (86%) with those in TB patients. A comprehensive pathway analysis revealed a potent activation of neutrophil and platelet mediated defenses including neutrophil and platelet degranulation, and NET formation at both time points. These pathways were also enriched in TB patients with high levels of lung damage compared to those with low. These findings suggest that neutrophils and platelets play a critical role in TB pathogenesis, and provide details of the timing of specific effector mechanisms that may contribute to TB lung pathology.

Indexed as

Mycobacterium tuberculosisTuberculosis, Lymph NodeHumansNeutrophil ActivationNeutrophilsPositron Emission Tomography Computed Tomography

Identifiers

PMID36454773
PMCPMC9714760
OpenAlexW4310507041

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.