PXD041950

PXD041950 is an original dataset announced via ProteomeXchange.

Title	The influence of highly effective modulator therapies on the sputum proteome in cystic fibrosis C4PR_LIV
Description	Cystic fibrosis (CF) is an inherited, multi-system disease caused by dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein, a ubiquitous ion channel important for epithelial hydration. A direct consequence of this dysfunction is impaired mucociliary clearance, chronic airway infection and a persistent neutrophilic inflammatory response that results in progressive loss of lung function, development of respiratory failure and premature death. Partial restoration of CFTR function is now possible for most CF patients through mutation specific CFTR modulators. Ivacaftor monotherapy produces significant clinical improvement in CF patients with the G511D mutation. Dual therapy, combining ivacaftor with lumacaftor or tezacaftor, results in modest clinical improvements in patients homozygous for F508del. More recently, triple therapy with elexacaftor/tezacaftor/ivacaftor (ETI) has led to dramatic improvements in lung function and quality of life in patients homozygous and heterozygous for F508del. Sputum proteomics is a powerful research technique capable of identifying important airway disease mechanisms by interrogating the proteome, an entire set of proteins within biological samples. It has confirmed the central role of neutrophilic immune dysregulation in CF and non-CF bronchiectasis, particularly involving the release of antimicrobial proteins and neutrophil-extracellular traps (NETs), and through impaired anti-inflammatory mechanisms. These processes produce distinct molecular signatures within the sputum proteome that become increasingly abnormal with chronic airway infection and progressive lung disease severity. In CF patients, airway and systemic inflammatory cytokines potentially related to these signatures reduce with the various forms of CFTR modulation. To date, no studies of ETI therapy in CF lung disease have assessed large-scale change in protein expression using untargeted proteomics. We hypothesised that ETI therapy would shift the sputum proteome toward health, potentially normalising airway biology in people with CF. The objectives of this study were to investigate changes in the CF sputum proteome with the introduction of ETI, correlate these with changes in clinical markers of disease severity, and make comparisons with the sputum proteome in healthy controls and in repeat samples from CF patients not suitable for ETI therapy. We also explored which molecular pathways associated with CF lung disease did not change with ETI.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:50:27.474.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD041950
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Rosie Maher
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-03 08:49:38	ID requested
⏵ 1	2023-11-14 09:50:27	announced

10.6019/PXD041950;

submitter keyword: sputum, modulator therapy,Cystic fibrosis, LC-MS/MS, elexacaftor/tezacaftor/ivacafto

Dr Edward Emmott
contact affiliation	Centre for Proteome Research, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK
contact email	E.Emmott@liverpool.ac.uk
lab head
Rosie Maher
contact affiliation	University of Liverpool
contact email	remaher@liverpool.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD041950
     1. Label: PRIDE project
     2. Name: The influence of highly effective modulator therapies on the sputum proteome in cystic fibrosis C4PR_LIV