Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study

  1. Brandes, Florian ORCID logo
  2. Märte, Melanie ORCID logo
  3. Buschmann, Dominik ORCID logo
  4. Meidert, Agnes ORCID logo
  5. Eggert, Marlene ORCID logo
  6. Langkamp, Markus
  7. Pridzun, Lutz
  8. Kirchner, Benedikt ORCID logo
  9. Billaud, Jean-Noël
  10. Amin, Nirav M.
  11. Pearson, Joseph C.
  12. Klein, Matthias ORCID logo
  13. Hauer, Daniela
  14. Gevargez Zoubalan, Clarissa
  15. Lindemann, Anja
  16. Choukér, Alexander ORCID logo
  17. Felbinger, Thomas W.
  18. Steinlein, Ortrud ORCID logo
  19. Pfaffl, Michael ORCID logo
  20. Kaufmann, Ines ORCID logo
  21. Schelling, Gustav ORCID logo

Download
s40635-021-00406-7.pdf 3,14MB
WeightNameValue
1000 Titel
  • Progranulin signaling in sepsis, community-acquired bacterial pneumonia and COVID-19: a comparative, observational study
1000 Autor/in
  1. Brandes, Florian |
  2. Märte, Melanie |
  3. Buschmann, Dominik |
  4. Meidert, Agnes |
  5. Eggert, Marlene |
  6. Langkamp, Markus |
  7. Pridzun, Lutz |
  8. Kirchner, Benedikt |
  9. Billaud, Jean-Noël |
  10. Amin, Nirav M. |
  11. Pearson, Joseph C. |
  12. Klein, Matthias |
  13. Hauer, Daniela |
  14. Gevargez Zoubalan, Clarissa |
  15. Lindemann, Anja |
  16. Choukér, Alexander |
  17. Felbinger, Thomas W. |
  18. Steinlein, Ortrud |
  19. Pfaffl, Michael |
  20. Kaufmann, Ines |
  21. Schelling, Gustav |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-09-03
1000 Erschienen in
1000 Quellenangabe
  • 9(1):43
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1186/s40635-021-00406-7 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412980/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Background!#!Progranulin 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.!##!Methods!#!The 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.!##!Results!#!Plasma 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.!##!Conclusions!#!Progranulin 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 registration!#!Clinicaltrials.gov registration number NCT03280576 Registered November 19, 2015.
1000 Sacherschließung
gnd 1206347392 COVID-19
lokal Progranulin
lokal Sensitivity
lokal Procalcitonin
lokal Specificity
lokal Sepsis
lokal Pneumonia
lokal COVID-19
lokal Gene networks
lokal Research Articles
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0003-3741-287X|https://orcid.org/0000-0002-0741-616X|https://orcid.org/0000-0003-0460-6459|https://orcid.org/0000-0002-5212-9071|https://orcid.org/0000-0002-9113-9643|https://frl.publisso.de/adhoc/uri/TGFuZ2thbXAsIE1hcmt1cw==|https://frl.publisso.de/adhoc/uri/UHJpZHp1biwgTHV0eg==|https://orcid.org/0000-0003-3878-0148|https://frl.publisso.de/adhoc/uri/QmlsbGF1ZCwgSmVhbi1Ob8OrbA==|https://frl.publisso.de/adhoc/uri/QW1pbiwgTmlyYXYgTS4=|https://frl.publisso.de/adhoc/uri/UGVhcnNvbiwgSm9zZXBoIEMu|https://orcid.org/0000-0001-9064-6865|https://frl.publisso.de/adhoc/uri/SGF1ZXIsIERhbmllbGE=|https://frl.publisso.de/adhoc/uri/R2V2YXJnZXogWm91YmFsYW4sIENsYXJpc3Nh|https://frl.publisso.de/adhoc/uri/TGluZGVtYW5uLCBBbmph|https://orcid.org/0000-0002-0133-4104|https://frl.publisso.de/adhoc/uri/RmVsYmluZ2VyLCBUaG9tYXMgVy4=|https://orcid.org/0000-0003-4311-6276|https://orcid.org/0000-0002-3192-1019|https://orcid.org/0000-0003-3556-0713|https://orcid.org/0000-0002-6538-0652
1000 Hinweis
  • DeepGreen-ID: 735094e75f8d46ac965a1af32121b91c ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Dateien
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6442092.rdf
1000 Erstellt am 2023-04-26T13:03:22.102+0200
1000 Erstellt von 322
1000 beschreibt frl:6442092
1000 Zuletzt bearbeitet Thu Oct 19 11:46:45 CEST 2023
1000 Objekt bearb. Thu Oct 19 11:46:45 CEST 2023
1000 Vgl. frl:6442092
1000 Oai Id
  1. oai:frl.publisso.de:frl:6442092 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source