PXD041007

PXD041007 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2023-03-21 08:14:42	ID requested
⏵ 1	2024-03-05 14:58:08	announced

10.6019/PXD041007;

submitter keyword: organ-on-chip,Proteomics, sepsis, neutrophils, immunosupression

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

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PRIDE project URI

• PRIDE
  1. PXD041007
     1. Label: PRIDE project
     2. Name: Distinct Immune Cell Functional Phenotypes in Sepsis Patients Correlates with Disease Severity