PXD041007 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Distinct Immune Cell Functional Phenotypes in Sepsis Patients Correlates with Disease Severity |
Description | Sepsis is a highly heterogeneous syndrome that impacts immune function and response to infection. To develop targeted therapeutics, immunophenotyping is needed to identify distinct immune cell functional phenotypes. Employing organ-on-chip for neutrophil functional analysis, we identified three distinct sepsis neutrophil phenotypes based on adhesion and migration patterns across human lung endothelial cells in response to cytokine activation (cytomix, TNF/IL-1β/IFNγ). The phenotypes were categorized as: a Hyperimmune phenotype characterized by enhanced cytomix-induced neutrophil adherence and migration, a Hypoimmune phenotype that was unresponsive to cytomix treatment, and a Hybrid phenotype with increased adherence but blunted migration in response to stimulation. Proteomic analysis identified both unique and shared proteins between the three phenotypes as compared to healthy controls. Proteins associated with neutrophil adherence were significantly upregulated in the Hyperimmune and Hybrid neutrophils, while the Hypoimmune group showed significant downregulation of these proteins. Clinically, the Hypoimmune group had significantly fewer patients requiring mechanical ventilation (29%) compared to the Hyperimmune group (70%). The Hypoimmune group and Hybrid group had significantly shorter ICU length of stay (LOS) than the Hyperimmune group. The Hypoimmune group also showed a trend for a lower mortality rate (35.7%) compared to the Hyperimmune group (50%). Thus, we identified associations between neutrophil phenotypes and important clinical outcomes, such as mechanical ventilation requirements, ICU LOS, and possibly mortality. Classification of sepsis patient phenotypes with diverse functional neutrophil responses and proteomic signatures can help distinguish patients who would benefit from specific treatments, such as immunosuppressive therapies and those who may be negatively impacted. |
HostingRepository | PRIDE |
AnnounceDate | 2024-03-05 |
AnnouncementXML | Submission_2024-03-05_14:58:07.988.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD041007 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Carmen Merali |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-03-21 08:14:42 | ID requested | |
⏵ 1 | 2024-03-05 14:58:08 | announced | |
Publication List
Keyword List
submitter keyword: organ-on-chip,Proteomics, sepsis, neutrophils, immunosupression |
Contact List
Salim Merali |
contact affiliation | Professor Temple University School of Pharmacy |
contact email | smerali@temple.edu |
lab head | |
Carmen Merali |
contact affiliation | Temple University |
contact email | clmerali@temple.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD041007
- Label: PRIDE project
- Name: Distinct Immune Cell Functional Phenotypes in Sepsis Patients Correlates with Disease Severity