ArticleEMBO molecular medicine2024
Highly secreted tryptophanyl tRNA synthetase 1 as a potential theranostic target for hypercytokinemic severe sepsis.
Article in EMBO molecular medicine, 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 14 papers.
What it found
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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.
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.
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Who cites it
14 citing papers in PubMed, 8 citations in OpenAlex.
- Uncovering drug-associated risk signals for neovascular age-related macular degeneration: an integrative pharmacovigilance and proteogenomic study.Eye (London, England) · 2026Article
- Human aminoacyl-tRNA synthetases as integrators of translation and cell signalling networks.Nature reviews. Molecular cell biology · 2026Review
- Integrative Proteomic Profiling of Blood Pressure and Hypertension.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Plasma extracellular vesicle proteomic analysis identifies WARS as a potential biomarker of infectious mononucleosis.BMC infectious diseases · 2026Article
- Plasma proteomics identifies early markers of endothelial and inflammatory activation associated with dengue disease severity in children.medRxiv : the preprint server for health sciences · 2026Article
- Transforming growth factor-β1 downregulates tryptophanyl-tRNA synthetase expression in human lung fibroblasts.Advances in medical sciences · 2026Article
- Beyond a metabolite: lactate and lactylation in lung diseases.Respiratory research · 2026Review
- Decreased expression of immune activator WARS1 and other pro-inflammatory mediators in type 1-like macrophages as an associated mode of action in response to fucoidan from marine brown algae.Frontiers in immunology · 2026Article
- A 107 Gene Nanostring Assay Effectively Translates the Cancer Genome Atlas, and Tumour Microenvironment Gastric Cancer Molecular Classification to a Patient-Derived Organoid Model.Genes, chromosomes & cancer · 2025Article
- Control of Overly Secreted Tryptophanyl tRNA Synthetase Attenuates Sepsis Severity in a Porcine Model.Biomolecules & therapeutics · 2025Article
- Comparative Analysis of HMC3 and C20 Microglial Cell Lines Reveals Differential Myeloid Characteristics and Responses to Immune Stimuli.Immunology · 2025Review
- The fibrin-derived peptide FX06 protects human pulmonary endothelial cells against the COVID-19-triggered cytokine storm.Frontiers in immunology · 2025Article
- Comprehensive Analysis of Selenium Metabolism and Selenoproteins-Associated Gene Signatures in Ulcerative Colitis.Journal of inflammation research · 2025Article
- The high-affinity tryptophan uptake transport system in human cells.Biochemical Society transactions · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
20 authors at 12 institutions in 2 countries.
Funding
Abstract
Despite intensive clinical and scientific efforts, the mortality rate of sepsis remains high due to the lack of precise biomarkers for patient stratification and therapeutic guidance. Secreted human tryptophanyl-tRNA synthetase 1 (WARS1), an endogenous ligand for Toll-like receptor (TLR) 2 and TLR4 against infection, activates the genes that signify the hyperinflammatory sepsis phenotype. High plasma WARS1 levels stratified the early death of critically ill patients with sepsis, along with elevated levels of cytokines, chemokines, and lactate, as well as increased numbers of absolute neutrophils and monocytes, and higher Sequential Organ Failure Assessment (SOFA) scores. These symptoms were recapitulated in severely ill septic mice with hypercytokinemia. Further, injection of WARS1 into mildly septic mice worsened morbidity and mortality. We created an anti-human WARS1-neutralizing antibody that suppresses proinflammatory cytokine expression in marmosets with endotoxemia. Administration of this antibody into severe septic mice attenuated cytokine storm, organ failure, and early mortality. With antibiotics, the antibody almost completely prevented fatalities. These data imply that blood-circulating WARS1-guided anti-WARS1 therapy may provide a novel theranostic strategy for life-threatening systemic hyperinflammatory sepsis.
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Registered trials
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.