The early-phase transcriptome and the clinical efficacy analysis in three modes of subcutaneous immunotherapy for allergic rhinitis

Huang, Jingyu; Zhang, Wei; Xiang, Rong; Tan, Lu; Liu, Peiqiang; Tao, Zezhang; Deng, Yuqin; Tong, Huan; Xu, Yu

doi:10.1016/j.waojou.2023.100811

Cited by 1 publication

(1 citation statement)

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“…To date, the mechanisms of hypersensitivity reactions that differentiate between respiratory and oral allergies from HVA have not been clarified. The most recent remarkable study by Huang et al performed on house dust mite-allergic patients treated with AIT, similarly to our study, revealed the significant downregulation of the innate immune response, the downregulation of NFκB and PPAR pathways, and a lower involvement of Th17 signalling with subsequent decreases in Th17 and Th2 cytokines [58]. Furthermore, a single-cell RNA analysis on grass pollen-allergic patients demonstrated the downregulation of genes associated with Th2 signalling and the downregulation of antigen-presenting pathways in B lymphocytes [34].…”

Section: Discussionsupporting

confidence: 90%

Blood Transcriptomics Identifies Multiple Gene Expression Pathways Associated with the Clinical Efficacy of Hymenoptera Venom Immunotherapy

Demšar Luzar,

Korošec,

Košnik

et al. 2024

IJMS

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Allergen-specific venom immunotherapy (VIT) is a well-established therapy for Hymenoptera venom allergy (HVA). However, the precise mechanism underlying its clinical effect remains uncertain. Our study aimed to identify the molecular mechanisms associated with VIT efficiency. We prospectively included 19 patients with HVA undergoing VIT (sampled before the beginning of VIT, after reaching the maintenance dose, one year after finishing VIT, and after a sting challenge) and 9 healthy controls. RNA sequencing of whole blood was performed on an Illumina sequencing platform. Longitudinal transcriptomic profiling revealed the importance of the inhibition of the NFκB pathway and the downregulation of DUX4 transcripts for the early protection and induction of tolerance after finishing VIT. Furthermore, successful treatment was associated with inhibiting Th2, Th17, and macrophage alternative signalling pathways in synergy with the inhibition of the PPAR pathway and further silencing of the Th2 response. The immune system became activated when reaching the maintenance dose and was suppressed after finishing VIT. Finally, successful VIT restores the immune system’s balance to a state similar to that of healthy individuals. Our results underline the important role of the inhibition of four pathways in the clinical effect of VIT: Th2, Th17, NFκB, and macrophage signalling. Two biomarkers specific for successful VIT, regardless of the time of sampling, were C4BPA and RPS10-NUDT3 and should be further tested as potential biomarkers.

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Section: Discussionsupporting

confidence: 90%