PXD041909-1

PXD041909 is an original dataset announced via ProteomeXchange.

Title	Serum proteomics hint at an early T-cell response and modulation of SARS-CoV-2-related pathogenic pathways in COVID-19-ARDS treated with Ruxolitinib
Description	Background: Acute respiratory distress syndrome (ARDS) in corona virus disease 19 (COVID-19) is triggered by hyperinflammation, thus providing a rationale for immunosuppressive treatments. The Janus kinase inhibitor Ruxolitinib (Ruxo) has shown efficacy in severe and critical COVID-19. In this study, we hypothesized that Ruxo's mode of action in this condition is reflected by changes in the peripheral blood proteome. Methods: This study included 11 COVID-19 patients, who were treated our center's Intensive Care Unit (ICU). All patients received standard-of-care treatment and n=8 patients with ARDS received Ruxo in addition. Blood samples were collected before (day 0) and on days 1, 6, and 10 of Ruxo treatment or, respectively, ICU admission. Serum proteomes were analyzed by mass spectrometry (MS) and cytometric bead array. Results: Linear modelling of MS data yielded 27 significantly differentially regulated proteins on day 1, 69 on day 6 and 72 on day 10. Only five factors (IGLV10-54, PSMB1, PGLYRP1, APOA5, WARS1) were regulated both concordantly and significantly over time. Overrepresentation analysis revealed biological processes involving T-cells only on day 1, while a humoral immune response and complement activation were detected at day 6 and day 10. Pathway enrichment analysis identified the NRF2-pathway early under Ruxo treatment and Network map of SARS-COV-2 signaling and Statin inhibition of cholesterol production at later time points. Conclusions: Our results indicate that the mechanism of action of Ruxo in COVID-19-ARDS can be related to both known effects of this drug as a modulator of T-cells and the SARS-CoV-2-infection.
HostingRepository	MassIVE
AnnounceDate	2023-05-03
AnnouncementXML	Submission_2023-05-03_05:30:12.500.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Johannes Graumann
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Acetyl; Carbamidomethyl
Instrument	Q Exactive Plus; Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-01 10:06:54	ID requested
⏵ 1	2023-05-03 05:30:12	announced

no publication

submitter keyword: SARS-CoV-2, COVID-19, Ruxolitinib, acute respiratory distress syndrome, proteomics

Elisabeth K.M. Mack
contact affiliation	Philipps-University Marburg and University Hospital Giessen and Marburg, Campus Marburg
contact email	elisabeth.mack@staff.uni-marburg.de
lab head
Chrysanthi Skevaki
contact affiliation	Institute of Laboratory Medicine, Philipps-University Marburg
contact email	Chrysanthi.Skevaki@uk-gm.de
lab head
Johannes Graumann
contact affiliation	Philipps-University Marburg
contact email	johannes.graumann@uni-marburg.de
dataset submitter

MassIVE dataset URI

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive.ucsd.edu/MSV000091706/