Analysis of cell-specific peripheral blood biomarkers in severe allergic asthma identifies innate immune dysfunction.
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ABSTRACT:
SUBMITTER: Nicholas B
PROVIDER: S-EPMC9804525 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
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Analysis of cell-specific peripheral blood biomarkers in severe allergic asthma identifies innate immune dysfunction.
Nicholas Ben B Guo Jane J Lee Hyun-Hee HH Bailey Alistair A de Waal Malefyt Rene R Cicmil Milenko M Djukanovic Ratko R
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 20220802 11
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Project description:BackgroundTranscriptomic analysis has been used to elucidate the complex pathogenesis of heterogeneous disease and may also contribute to identify potential therapeutic targets by delineating the hub genes. This study aimed to investigate whether blood transcriptomic clustering can distinguish clinical and immune phenotypes of asthmatics, and microbiome in asthmatics.MethodsTranscriptomic expression of peripheral blood mononuclear cells (PBMCs) from 47 asthmatics and 21 non-asthmatics was measured using RNA sequencing. A hierarchical clustering algorithm was used to classify asthmatics. Differentially expressed genes, clinical phenotypes, immune phenotypes, and microbiome of each transcriptomic cluster were assessed.ResultsIn asthmatics, three distinct transcriptomic clusters with numerously different transcriptomic expressions were identified. The proportion of severe asthmatics was highest in cluster 3 as 73.3%, followed by cluster 2 (45.5%) and cluster 1 (28.6%). While cluster 1 represented clinically non-severe T2 asthma, cluster 3 tended to include severe non-T2 asthma. Cluster 2 had features of both T2 and non-T2 asthmatics characterized by the highest serum IgE level and neutrophil-dominant sputum cell population. Compared to non-asthmatics, cluster 1 showed higher CCL23 and IL1RL1 expression while the expression of TREML4 was suppressed in cluster 3. CTSD and ALDH2 showed a significant positive linear relationship across three clusters in the order of cluster 1 to 3. No significant differences in the diversities of lung and gut microbiomes were observed among transcriptomic clusters of asthmatics and non-asthmatics. However, our study has limitations in that small sample size data were analyzed with unmeasured confounding factors and causal relationships or function pathways were not verified.ConclusionsGenetic clustering based on the blood transcriptome may provide novel immunological insight, which can be biomarkers of asthma immune phenotypes. Trial registration Retrospectively registered.
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