ArticleIntensive care medicine experimental2021
Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study.
Article in Intensive care medicine experimental, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03280576 (Sensitivity and Specificity of Progranulin as a Biomarker for Sepsis), which is not on this map. Cited by 14 papers, 2 of them syntheses that pooled it.
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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.
Sensitivity and Specificity of Progranulin as a Biomarker for Sepsis
Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- S100 Protein and Interleukin Biomarkers Among COVID-19 Subjects With and Without Pneumonia: A Systematic Review and Meta-Analysis.British journal of biomedical science · 2025Pooled it
- Organokines in COVID-19: A Systematic Review.Cells · 2023Pooled it
- GRN and KLRB1 define a shared peripheral-blood transcriptomic signature linking SLE and IPF.Journal of translational autoimmunity · 2026Article
- Progranulin Is a Useful Biomarker to Predict Mortality in ICU Patients with Low Burden of Organ Dysfunction.Biomedicines · 2026Article
- Distinguishing Between Bacterial and Viral Community-Acquired Pneumonia in Hospitalized Adults: The Importance of Clinical, Laboratory, and Imaging Findings.Pulmonary medicine · 2026Article
- A deep generative model for deciphering cellular dynamics and in silico drug discovery in complex diseases.Nature biomedical engineering · 2025Article
- Opposing role of phagocytic receptors MERTK and AXL in Progranulin deficient FTD.Communications biology · 2025Article
- Article
- Detecting global and local hierarchical structures in cell-cell communication using CrossChat.Nature communications · 2024Article
- Progranulin: A promising biomarker and therapeutic target for fibrotic diseases.Acta pharmaceutica Sinica. B · 2024Review
- Extensive blood transcriptome analysis reveals cellular signaling networks activated by circulating glycocalyx components reflecting vascular injury in COVID-19.Frontiers in immunology · 2023Article
- High Serum Progranulin Levels in COVID-19 Patients: A Pilot Study.Biochemistry. Biokhimiia · 2022Article
- Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study.Frontiers in immunology · 2022Article
- Extracellular Vesicle Associated miRNAs Regulate Signaling Pathways Involved in COVID-19 Pneumonia and the Progression to Severe Acute Respiratory Corona Virus-2 Syndrome.Frontiers in immunology · 2021Article
Corrections and comments
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Authors and funding
21 authors.
Funding
Abstract
backgroundProgranulin is a widely expressed pleiotropic growth factor with a central regulatory effect during the early immune response in sepsis. Progranulin signaling has not been systematically studied and compared between sepsis, community-acquired pneumonia (CAP), COVID-19 pneumonia and a sterile systemic inflammatory response (SIRS). We delineated molecular networks of progranulin signaling by next-generation sequencing (NGS), determined progranulin plasma concentrations and quantified the diagnostic performance of progranulin to differentiate between the above-mentioned disorders using the established biomarkers procalcitonin (PCT), interleukin-6 (IL-6) and C-reactive protein (CRP) for comparison.
methodsThe diagnostic performance of progranulin was operationalized by calculating AUC and ROC statistics for progranulin and established biomarkers in 241 patients with sepsis, 182 patients with SIRS, 53 patients with CAP, 22 patients with COVID-19 pneumonia and 53 healthy volunteers. miRNAs and mRNAs in blood cells from sepsis patients (n = 7) were characterized by NGS and validated by RT-qPCR in an independent cohort (n = 39) to identify canonical gene networks associated with upregulated progranulin at sepsis onset.
resultsPlasma concentrations of progranulin (ELISA) in patients with sepsis were 57.5 (42.8-84.9, Q25-Q75) ng/ml and significantly higher than in CAP (38.0, 33.5-41.0 ng/ml, p < 0.001), SIRS (29.0, 25.0-35.0 ng/ml, p < 0.001) and the healthy state (28.7, 25.5-31.7 ng/ml, p < 0.001). Patients with COVID-19 had significantly higher progranulin concentrations than patients with CAP (67.6, 56.6-96.0 vs. 38.0, 33.5-41.0 ng/ml, p < 0.001). The diagnostic performance of progranulin for the differentiation between sepsis vs. SIRS (n = 423) was comparable to that of procalcitonin. AUC was 0.90 (95% CI = 0.87-0.93) for progranulin and 0.92 (CI = 0.88-0.96, p = 0.323) for procalcitonin. Progranulin showed high discriminative power to differentiate bacterial CAP from COVID-19 (sensitivity 0.91, specificity 0.94, AUC 0.91 (CI = 0.8-1.0) and performed significantly better than PCT, IL-6 and CRP. NGS and partial RT-qPCR confirmation revealed a transcriptomic network of immune cells with upregulated progranulin and sortilin transcripts as well as toll-like-receptor 4 and tumor-protein 53, regulated by miR-16 and others.
conclusionsProgranulin signaling is elevated during the early antimicrobial response in sepsis and differs significantly between sepsis, CAP, COVID-19 and SIRS. This suggests that progranulin may serve as a novel indicator for the differentiation between these disorders.
trial registrationClinicaltrials.gov registration number NCT03280576 Registered November 19, 2015.
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