Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis - a potential biomarker role for LysoPC.

Rindlisbacher, Barbara; Schmid, Cornelia; Geiser, Thomas; Bovet, Cédric; Funke-Chambour, Manuela (2018). Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis - a potential biomarker role for LysoPC. Respiratory research, 19(1), p. 7. BioMed Central 10.1186/s12931-018-0714-2

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BACKGROUND Idiopathic pulmonary fibrosis (IPF) is a lethal lung disease of unknown etiology. Patients present loss of lung function, dyspnea and dry cough. Diagnosis requires compatible radiologic imaging and, in undetermined cases, invasive procedures such as bronchoscopy and surgical lung biopsy. The pathophysiological mechanisms of IPF are not completely understood. Lung injury with abnormal alveolar epithelial repair is thought to be a major cause for activation of profibrotic pathways in IPF. Metabolic signatures might indicate pathological pathways involved in disease development and progression. Reliable serum biomarker would help to improve both diagnostic approach and monitoring of drug effects. METHOD The global metabolic profiles measured by ultra high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) of ten stable IPF patients were compared to the ones of ten healthy participants. The results were validated in an additional study of eleven IPF patients and ten healthy controls. RESULTS We discovered 10 discriminative metabolic features using multivariate and univariate statistical analysis. Among them, we identified one metabolite at a retention time of 9.59 min that was two times more abundant in the serum of IPF patients compared to healthy participants. Based on its ion pattern, a lysophosphatidylcholine (LysoPC) was proposed. LysoPC is a precursor of lysophosphatidic acid (LPA) - a known mediator for lung fibrosis with its pathway currently being evaluated as new therapeutic drug target for IPF and other fibrotic diseases. CONCLUSIONS We identified a LysoPC by UHPLC-HRMS as potential biomarker in serum of patients with IPF. Further validation studies in a larger cohort are necessary to determine its role in IPF. TRIAL REGISTRATION Serum samples from IPF patients have been obtained within the clinical trial NCT02173145 at baseline and from the idiopathic interstitial pneumonia (IIP) cohort study. The study was approved by the Swiss Ethics Committee, Bern (KEK 002/14 and 246/15 or PB_2016-01524).

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology

UniBE Contributor:

Geiser, Thomas; Bovet, Cédric and Funke-Chambour, Manuela

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1465-9921

Publisher:

BioMed Central

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

04 Feb 2019 15:12

Last Modified:

10 Feb 2019 02:38

Publisher DOI:

10.1186/s12931-018-0714-2

PubMed ID:

29321022

Uncontrolled Keywords:

High-resolution mass spectrometry Idiopathic pulmonary fibrosis Lysophosphatidylcholine Metabolomics Serum Ultra high-performance liquid chromatography

BORIS DOI:

10.7892/boris.123222

URI:

https://boris.unibe.ch/id/eprint/123222

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