Clinical and Experimental Allergy最新文献

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.

The cover image is based on the article Epidemiology, Diagnosis and Prevention of Allergic Rhinitis in High-Pollen Areas of Northern China by T. T. Ma et al., https://doi.org/10.1111/cea.70087.

The last decades have shown the number of subjects developing allergic rhinitis (AR), allergic asthma (AA), atopic dermatitis (AD), and food allergy rose continuously worldwide. To cure these allergic diseases, allergen-specific immunotherapy (AIT) represents the unique treatment capable of providing clinical outcomes through the induction of long-term immunological tolerance. Despite proven efficacy, the duration of treatment, AIT-associated side effects, and the difficulty in identifying potential responders by diagnosis lead to poor patient compliance. Clinical investigations evidenced the role of blocking IgG antibodies induced by AIT in long-term tolerance. These observations suggested that passive allergy immunotherapy (PAIT) with low doses of allergen-specific blocking IgG antibodies represents an elegant alternative to frequent administrations of allergen extracts. Tremendous technological progress in the discovery/production of fully human monoclonal antibodies (mAbs) with very low immunogenicity has been made in the last decades, and these therapeutic antibodies revolutionised the treatment of cancers or infectious diseases. The recent advances in the isolation of rare allergen-specific IgE+ B cells and the generation of human antibodies in transgenic mice made possible the production of human monoclonal blocking antibodies against any allergen, sharing the same affinity with the corresponding naturally occurring IgE. This comprehensive review will describe the first promising preclinical and clinical data obtained with antibody cocktails targeting several IgE epitopes to some key single allergens. PAIT is safe and effective for the downregulation of the allergic response. Compared with conventional extract-based AIT, the positive outcomes could require much less dosing.

Heterogeneity among CRSwNP patients in Western and Eastern countries leads to differences in management. Type 2 (T2) inflammation accounts for the majority of CRSwNP patients in Western countries, while non-T2 inflammation is the main endotype in CRSwNP patients in Eastern countries. Precise identification of T2 inflammation holds significant promise for optimising treatment outcomes. The treatment of T2 inflammation-biased CRSwNP primarily involves glucocorticoids, reboot surgery, and T2 biologics, while non-T2 inflammation-dominant CRSwNP is mainly treated with macrolide antibiotics.