Abstract
Background: Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy. This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. Methods: We performed whole-transcriptome RNA sequencing on peripheral blood of 30 non-atopic non-asthmatic controls and 30 asthmatic patients. A quantitative PCR (qPCR) validation study of PTGDR2 that encodes for CRTH2 receptor, expressed in cells involved in T2 inflammation, was developed in a cohort of 361 independent subjects: 94 non-asthmatic non-atopic controls, 187 asthmatic patients [including 82 with chronic rhinosinusitis with nasal polyposis (CRSwNP) and 24 with aspirin-exacerbated respiratory disease (AERD)], 52 with allergic rhinitis, and 28 with CRSwNP without asthma. Results: PTGDR2 was one of the most differentially overexpressed genes in asthmatic patients’ peripheral blood (p-value 2.64 × 106). These results were confirmed by qPCR in the validation study, where PTGDR2 transcripts were significantly upregulated in asthmatic patients (p < 0.001). This upregulation was mainly detected in some subgroups such as allergic asthma, asthma with CRSwNP, AERD, eosinophilic asthma, and severe persistent asthma. PTGDR2 expression was detected in different blood cell types, and its correlation with eosinophil counts showed differences in some groups of asthmatic patients. Conclusions: We found that PTGDR2 expression levels could identify asthma patients, introduce a minimally invasive biomarker for adult asthma molecular phenotyping, and add additional information to blood eosinophils. Although further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists.
Highlights
Asthma is a heterogeneous disease, characterized by chronic airway inflammation with variable respiratory symptoms, affecting around 358 million people worldwide [1,2]
A total of 421 subjects participated in the study, including 60 subjects who participated in the transcriptomic analysis, and 94 controls and 267 patients involved in the validation study
We found that PTGDR2 was not differently expressed in patients with allergic rhinitis without concomitant asthma, indicating that the levels of PTGDR2 in peripheral blood might help differentiate allergic patients with and without asthma
Summary
Asthma is a heterogeneous disease, characterized by chronic airway inflammation with variable respiratory symptoms, affecting around 358 million people worldwide [1,2]. Some whole-genome expression studies in blood cells have analyzed the effect of asthma severity [12,13] In another transcriptomic study, the samples of PBMCs from 118 adult asthmatics were analyzed between the stable and exacerbation states, showing a distinct exacerbation-associated gene expression signature [14]. The effect of the biological treatment benralizumab on the whole blood transcriptomic signature of severe asthmatic patients was analyzed, showing significant reductions in the expression of genes associated with eosinophilic inflammatory responses [15]. Precision medicine is a promising strategy to identify biomarkers, stratify asthmatic patients according to different endotypes, and match them with the appropriate therapy This proof-of-concept study aimed to investigate whether gene expression in peripheral blood could provide a valuable noninvasive approach for the molecular phenotyping of asthma. Further studies are required, analyzing PTGDR2 expression levels in peripheral blood of asthmatics might assist in selecting patients for treatment with specific antagonists
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