The online version of this article (doi: https://doi.org/10.1186/s12931-018-0714-2) contains supplementary material, which is available to authorized users.
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.
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.
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.
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.
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).
Additional file 1: Figure S1. Heat maps representing the log10-transformed abundance profile (Pareto scaled) of the regulated metabolic features isolated by multivariate and/or univariate statistical analysis in the (top) pilot study and (bottom) validation study. Identity (summarized by the retention time followed by the corresponding m/z ratio or neutral mass n) of the metabolic features are shown on the right side. Cells colored in red represent up-regulated, colored in blue down-regulated abundances. The analysis was done with the MetaboAnalyst online platform [ 59]. (PNG 581 kb)
Additional file 2: Figure S2. MS (top, HDMSE experiment) and MS/MS spectra (bottom, HDMSE experiment) of the metabolic features eluting at 5.9 min acquired in the positive ESI mode and potentially assigned to the [M + H]+ 3-hydroxydecanoyl carnitine ion. The detection of the characteristic acylcarnitine fragment [C4H5O2]+ at m/z 85.0284 was confirmed by MS/MS spectra (bottom, HDMSE experiment). (PDF 99 kb)12931_2018_714_MOESM2_ESM.pdf
Additional file 3: Figure S3. MS/MS spectra (DDA experiments) of the metabolic features eluting at 9.6 min acquired in the (a) positive and (b) negative ESI mode and potentially assigned to the [M + H]+ and [M + CHOO]− LysoPC ions, respectively. The main fragments are annotated with the corresponding structure, measured m/z ratio and mass accuracy. (PDF 150 kb)12931_2018_714_MOESM3_ESM.pdf
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- Serum metabolic profiling identified a distinct metabolic signature in patients with idiopathic pulmonary fibrosis – a potential biomarker role for LysoPC
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