Evidence map›Paper›PMID 31280495›Full record

Trial reportJournal of leukocyte biology2019

Leukocyte transcriptional signatures dependent on LPS dosage in human endotoxemia.

Hina N Khan, Desiree Perlee, Lieke Schoenmaker, Anne-Jan van der Meer, Marek Franitza, Mohammad Reza Toliat, Peter Nürnberg, Aeilko H Zwinderman, Tom van der Poll, Brendon P Scicluna

Open access · hybridAbstract readClinical Trial
In one paragraph

Trial report in Journal of leukocyte biology, 2019. 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
1.0field-weighted citation impact, top 24% 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, 21 citations in OpenAlex.

  1. Guideline
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  8. KLF4 is an epigenetically modulated, context-dependent tumor suppressor.Frontiers in cell and developmental biology · 2024
    Review
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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

10 authors at 3 institutions in 2 countries.

Hina N KhanCenter for Experimental Molecular Medicine, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Desiree PerleeCenter for Experimental Molecular Medicine, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Lieke SchoenmakerCenter for Experimental Molecular Medicine, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Anne-Jan van der MeerCenter for Experimental Molecular Medicine, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-0520-0816
Marek FranitzaCologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
Mohammad Reza ToliatCologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
Peter NürnbergCologne Center for Genomics (CCG), University of Cologne, Cologne, Germany.
Aeilko H ZwindermanDepartment of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam University Medical Centers, Academic Medical Center, Amsterdam, The Netherlands.
Tom van der PollCenter for Experimental Molecular Medicine, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Brendon P SciclunaCenter for Experimental Molecular Medicine, Amsterdam University Medical Centers, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
University of Amsterdam · NLAmsterdam UMC Location University of Amsterdam · NLUniversity of Cologne · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The host immune response is characterized by a complex interplay of signal-specific cellular transcriptional responses. The magnitude of the immune response is dependent on the strength of the external stimulus. Knowledge on leukocyte transcriptional responses altered in response to different stimulus dosages in man is lacking. Here, we sought to identify leukocyte transcriptional signatures dependent on LPS dose in humans. Healthy human volunteers were administered 1 ng/kg (n = 7), 2 ng/kg (n = 6), or 4 ng/kg (n = 7) LPS intravenously. Blood was collected before (pre-LPS) and 4 h after LPS administration. Total RNA was analyzed by microarrays and generalized linear models. Pathway analysis was performed by using Ingenuity pathway analysis. Leukocyte transcriptomes altered per LPS dosage were predominantly shared, with 47% common signatures relative to pre-LPS. A univariate linear model identified a set of 3736 genes that exhibited a dependency on differing LPS dosages. Neutrophil, monocyte, and lymphocyte counts explained 38.9% of the variance in the LPS dose-dependent gene set. A multivariate linear model including leukocyte composition delineated a set of 295 genes with a dependency on LPS dose. Evaluation of the 295 gene signature in patients with sepsis due to abdominal infections showed significant correlations. Promoter regions of the LPS dose gene set were enriched for YY1, EGR1, ELK1, GABPA, KLF4, and REL transcription factor binding sites. Intravenous injection of 1, 2, or 4 ng/kg LPS was accompanied by both shared and distinct leukocyte transcriptional alterations. These data may assist in assessing the severity of the insult in patients with abdominal sepsis.

Indexed as

EndotoxemiaGene Expression ProfilingLeukocytesAdultDose-Response Relationship, ImmunologicGene Expression RegulationHumansKruppel-Like Factor 4LipopolysaccharidesMaleOligonucleotide Array Sequence AnalysisTranscription, GeneticKLF4 protein, humanKruppel-Like Factor 4Lipopolysaccharidesbloodgenomicsimmune response

Identifiers

PMID31280495
PMCPMC6852106
OpenAlexW2955630914

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.