Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology · 2025
Longitudinal Blood Transcriptome Analysis Reveals Dynamic Gene Expression Patterns in Patients With Allergic Rhinitis Following House Dust Mite Subcutaneous Immunotherapy.
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Liu Chang, He Shikun, Zhang Jinxiu, Zhu Jincai, Rao Jianxia, Wang Kanghua, Fan Yunping, Sun Yueqi
Аннотация
INTRODUCTION: Subcutaneous immunotherapy (SCIT) is a well-established treatment for inducing immune tolerance in patients with allergic rhinitis (AR). However, the precise molecular mechanisms by which SCIT induces immune tolerance, particularly at the transcriptomic level over the treatment course, have not been fully elucidated. This study aimed to investigate the molecular mechanisms of SCIT by analysing changes in peripheral blood gene expression profiles in AR patients over time.
METHODS: Whole blood samples were prospectively collected from 30 AR patients (16 paediatric, 14 adult) and 10 healthy controls. RNA sequencing was performed at baseline and at 3, 6 and 12 months of SCIT. Differentially expressed genes (DEGs) were identified, and pathway enrichment, immune cell deconvolution and weighted gene co-expression network analysis were conducted to explore immune regulation and tolerance mechanisms.
RESULTS: AR patients showed 1180 DEGs compared to healthy controls, with upregulated genes related to B-cell activation and downregulated genes linked to Th1 differentiation. Both paediatric and adult cohorts exhibited consistent transcriptomic changes, characterised by progressive normalisation of gene expression, with the number of DEGs decreasing over time and significant convergence towards healthy control profiles by 12 months. SCIT enhanced type I interferon responses and antiviral pathways while reducing B-cell activation and inflammatory responses. Immune cell analysis revealed increased regulatory T cells and dendritic cells by 6 months and reduced Th2 cells and eosinophils by 12 months. Key immune-related hub genes, including CD19, CD79A, CD79B, CD22, IFIH1, STAT1, DHX58, TLR4, IL1B and TLR1, were identified as central to SCIT efficacy.
CONCLUSION: SCIT dynamically modulates blood gene expression profiles in AR patients, inducing immune tolerance and reducing inflammatory responses. These findings enhance understanding of the molecular mechanisms of SCIT and highlight potential biomarkers for predicting and monitoring treatment efficacy.
METHODS: Whole blood samples were prospectively collected from 30 AR patients (16 paediatric, 14 adult) and 10 healthy controls. RNA sequencing was performed at baseline and at 3, 6 and 12 months of SCIT. Differentially expressed genes (DEGs) were identified, and pathway enrichment, immune cell deconvolution and weighted gene co-expression network analysis were conducted to explore immune regulation and tolerance mechanisms.
RESULTS: AR patients showed 1180 DEGs compared to healthy controls, with upregulated genes related to B-cell activation and downregulated genes linked to Th1 differentiation. Both paediatric and adult cohorts exhibited consistent transcriptomic changes, characterised by progressive normalisation of gene expression, with the number of DEGs decreasing over time and significant convergence towards healthy control profiles by 12 months. SCIT enhanced type I interferon responses and antiviral pathways while reducing B-cell activation and inflammatory responses. Immune cell analysis revealed increased regulatory T cells and dendritic cells by 6 months and reduced Th2 cells and eosinophils by 12 months. Key immune-related hub genes, including CD19, CD79A, CD79B, CD22, IFIH1, STAT1, DHX58, TLR4, IL1B and TLR1, were identified as central to SCIT efficacy.
CONCLUSION: SCIT dynamically modulates blood gene expression profiles in AR patients, inducing immune tolerance and reducing inflammatory responses. These findings enhance understanding of the molecular mechanisms of SCIT and highlight potential biomarkers for predicting and monitoring treatment efficacy.