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Clusterization of patients with idiopathic pulmonary fibrosis with chemokine receptors: a possible role in the diagnostic work-up of idiopathic pulmonary fibrosis?

ABSTRACT: Background and objective: Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease whose diagnosis often requires surgical lung biopsies (SLB) in cases without consistent radiological findings. We previously published that the expression of the chemokine receptors CXCR3 and CCR4 on T cells is significantly different in bronchoalveolar lavage (BAL) of IPF patients from other interstitial lung diseases. The aim of the study was to evaluate cut-off values of CXCR3 and CCR4 receptors expressed on bronchoalveolar lavage (BAL) and peripheral blood (PB) T cells useful for a differential diagnosis. Methods: Ninety-three patients were enrolled: 35 IPF, 36 interstitial lung diseases (nIPF) and 22 sarcoidosis. CXCR3 and CCR4 were evaluated on BAL and PB T lymphocytes with flow cytometry. Results: Among PB and BAL variables considered, the values of the ratio of BAL and PB CXCR3 on CD4 cells were clustered in the most informative way to obtain a classification rule for the diagnosis of patients without steroid therapy (n = 66/93). Patients with a CXCR3 ratio BAL/PB on CD4 T cells lower or equal than 1.43 were assigned to the IPF group with sensitivity = 0.87 and specificity = 0.90. All the other variables considered showed lower sensitivity and specificity in discriminating IPF patients. Conclusions: The evaluation of chemokine receptors on BAL and PB T lymphocytes could aid to discriminate IPF in subjects without steroid therapy, particularly in those patients with a high-resolution computed tomography (HRCT) non typical for Usual Interstitial Pneumonia (UIP). (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 35-43).

SUBMITTER: Brunetti G

PROVIDER: S-EPMC7170056 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Clusterization of patients with idiopathic pulmonary fibrosis with chemokine receptors: a possible role in the diagnostic work-up of idiopathic pulmonary fibrosis?

Brunetti Giuseppe G Malovini Alberto A Testoni Claudia C Bellazzi Riccardo R Balestrino Antonella A Meriggi Antonio A Moscato Gianna G Alessandrini Arnaldo A Rivolta Federica F Pignatti Patrizia P

Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG 20180428 1

<i>Background and objective:</i> Idiopathic pulmonary fibrosis (IPF) is a chronic and irreversible interstitial lung disease whose diagnosis often requires surgical lung biopsies (SLB) in cases without consistent radiological findings. We previously published that the expression of the chemokine receptors CXCR3 and CCR4 on T cells is significantly different in bronchoalveolar lavage (BAL) of IPF patients from other interstitial lung diseases. The aim of the study was to evaluate cut-off values o ...[more]

PMID: 32476878

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Project description:Background Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease with limited therapeutic options. Recent studies have demonstrated that chemokines play a vital role in IPF pathogenesis. In the present study, we explored whether the gene signature associated with chemokines could be used as a reliable biological marker for patients with IPF. Methods Chemokine-related differentially expressed genes (CR-DEGs) in IPF and control lung tissue samples were identified using data from the Gene Expression Omnibus database. A chemokine-related signature of the diagnostic model was established using the LASSO-Cox regression. In addition, unsupervised cluster analysis was conducted using consensus-clustering algorithms. The CIBERSORT algorithm was used to calculate immune cell infiltration across patient subgroups. Finally, we established a mouse model of bleomycin-induced pulmonary fibrosis and a model of fibroblasts treated with TGFβ1. Expression levels of chemokine-related signature genes were determined using real-time quantitative polymerase chain reaction (RT-qPCR). Results We established a chemokine-related eleven-gene signature of a diagnostic model consisting of CXCL2, CCRL2, ARRB1, XCL1, GRK5, PPBP, CCL19, CCL13, CCL11, CXCL6, and CXCL13, which could easily distinguish between IPF patients and controls. Additionally, we identified two subtypes of IPF samples based on chemokine-related gene expression. Pulmonary function parameters and stromal scores were significantly higher in subtype 1 than in subtype 2. Several immune cell types, especially plasma cells and macrophages, differ significantly between the two subtypes. RT-qPCR results showed that the expression levels of Cxcl2 and Ccl2 increased considerably in bleomycin-induced mice. Meanwhile, Arrb1, Ccrl2, Grk5, and Ppbp expression was significantly reduced. Furthermore, multiple chemokine-related genes were altered in TGFβ1 or TNFα-induced fibroblast cells. Conclusions A novel chemokine-related eleven-signature of diagnostic model was developed. These genes are potential biomarkers of IPF and may play essential roles in its pathogenesis.

Dataset Information

Clusterization of patients with idiopathic pulmonary fibrosis with chemokine receptors: a possible role in the diagnostic work-up of idiopathic pulmonary fibrosis?

Publications

Clusterization of patients with idiopathic pulmonary fibrosis with chemokine receptors: a possible role in the diagnostic work-up of idiopathic pulmonary fibrosis?

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