PXD071549-1

PXD071549 is an original dataset announced via ProteomeXchange.

Title	Systemic effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the plasma and serum proteome
Description	Cystic fibrosis (CF), resulting from a dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR), affects multiple organs through mucus obstruction and differences in secretion. The CFTR modulator drug combination elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, ETI) has markedly improved clinical symptoms, but its broader molecular and systemic effects remain to be fully elucidated. We employed mass spectrometry-based proteomics to compare the plasma and serum proteomes of person with CF (pwCF) treated with the earlier, less effective lumacaftor/ivacaftor (LUM/IVA) combination against those receiving the more potent ELX/TEZ/IVA therapy. Our analysis revealed both specific and common pharmacodynamic signatures associated with inflammation and metabolic processes under each treatment regimen. Notably, ELX/TEZ/IVA therapy exhibited more consistent alterations across pwCF that were directed towards profiles observed in healthy individuals. Furthermore, by comparing sputum and serum proteomes of ELX/TEZ/IVA treated pwCF we identified counter directional changes in the pulmonary surfactant-associated protein B, SFTPB, a potential biomarker of lung permeability, which also correlated with lung function improvements and could be validated in an independent cohort. This study provides a comprehensive resource that enhances our understanding of CFTR modulator-driven proteome alterations, offering insights to both systemic and local protein regulation in CF. Our findings indicate that ELX/TEZ/IVA promotes broader systemic health improvements, providing critical insights that could shape future therapeutic strategies in CF.
HostingRepository	PRIDE
AnnounceDate	2026-04-14
AnnouncementXML	Submission_2026-04-14_10:31:37.789.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Marieluise Kirchner
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; deamidated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Astral; Q Exactive HF-X

Revision	Datetime	Status	ChangeLog Entry
0	2025-12-03 16:19:43	ID requested
⏵ 1	2026-04-14 10:31:38	announced

10.1016/j.cels.2026.101569;

Fentker K, Kirchner M, Ziehm M, Niquet S, Popp O, Duerr J, Schaupp L, Roehmel J, Thee S, H, ä, mmerling S, Sommerburg O, Stahl M, Graeber SY, Mall MA, Mertins P, Systemic effects of cystic fibrosis transmembrane conductance regulator modulators on the plasma and serum proteome. Cell Syst, 17(5):101569(2026) [pubmed]

submitter keyword: Serum, Cystic fibrosis, ELX/TEZ/IVA, Plasma,Astral, DDA, CFTR modulator, DIA, HFX, LUM/IVA,human, Sputum, label free

Philipp Mertins
contact affiliation	Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany. Berlin Institute of Health (BIH), Berlin, Germany.
contact email	Philipp.mertins@mdc-berlin.de
lab head
Marieluise Kirchner
contact affiliation	Proteomics Platform, BIH@Charite
contact email	marieluise.kirchner@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD071549
     1. Label: PRIDE project
     2. Name: Systemic effects of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on the plasma and serum proteome