Subcutaneous Allergen-Specific Immunotherapy for Allergic Rhinitis: Divergent IgA Responses in Nasal Mucosa and Blood With Validation of B Cell Class-Switching in Lymph Nodes and Blood

IF 4 2区医学 Q2 ALLERGY

Clinical and Translational Allergy Pub Date : 2025-09-02 DOI:10.1002/clt2.70097

Maryam Jafari, Marianne Petro, Eirini Paziou, Eric Hjalmarsson, Agnetha Karlsson, Monika Ezerskyte, Laila Hellkvist, Susanna Kumlien Georén, Eduardo I. Cardenas, Lars-Olaf Cardell

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引用次数: 0

Abstract

Background

Subcutaneous immunotherapy (SCIT) has been a cornerstone treatment for allergic rhinitis (AR) for over 50 years, consistently demonstrating symptom reduction and modulation of immune responses. Despite this, the underlying mechanisms responsible for the efficacy of SCIT remain incompletely understood, especially with regard to local immune responses in lymph nodes and nasal mucosa.

Aim

To determine the impact of SCIT treatment on immunoglobulin production in blood and nasal mucosa, as well as B cell class-switching in blood and lymph nodes.

Methodology

Blood, nasal lavage (NAL), and fine-needle aspirates (FNA) of inguinal lymph nodes were collected from 23 patients with birch and/or timothy pollen-induced AR before and after SCIT updosing. General response to SCIT was evaluated with symptom and medication scores, as well as allergen-mediated activation of basophils. Allergen-specific IgE, IgA, IgG, and IgG4 were measured in blood and NAL via ELISA. B-cell class-switching was assessed in blood and FNAs by flow cytometry.

Results

AR symptoms, medication use, and basophil sensitivity to allergens was reduced after SCIT updosing. Interestingly, the plasma levels of allergen-specific IgA, IgG, and IgG4 increased after SCIT updosing, while the levels of allergen-specific IgE and IgA decreased in NAL at this timepoint. Moreover, these results were accompanied by an increase in conventional (IgD⁻CD27⁺) and unconventional (IgD⁻CD27⁻) memory B cells in blood and lymph nodes, respectively.

Conclusion

This study highlights the differential effects of SCIT on local and systemic immunity and identifies early immunological changes associated with treatment. However, confirmation of long-term tolerance will require extended follow-up, including in-season analyses. The local decrease in allergen-specific IgA in NAL, alongside a systemic increase in allergen-specific IgA and IgG4, underscores the importance of assessing both mucosal and systemic responses when evaluating SCIT efficacy.

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变应性鼻炎的皮下过敏原特异性免疫治疗：鼻黏膜和血液中不同的IgA反应与淋巴结和血液中B细胞类型转换的验证

50多年来，皮下免疫治疗（SCIT）一直是变应性鼻炎（AR）的基础治疗方法，一直显示出症状减轻和免疫反应调节。尽管如此，SCIT疗效的潜在机制仍然不完全清楚，特别是关于淋巴结和鼻黏膜的局部免疫反应。目的探讨SCIT治疗对血液和鼻黏膜免疫球蛋白产生以及血液和淋巴结B细胞类型转换的影响。方法收集23例白桦和/或timothym花粉诱导的AR患者在SCIT治疗前后的血液、鼻灌洗（NAL）和腹股沟淋巴结细针抽吸（FNA）。通过症状和药物评分以及过敏原介导的嗜碱性粒细胞激活来评估对SCIT的一般反应。采用ELISA法检测血液和NAL中过敏原特异性IgE、IgA、IgG和IgG4。通过流式细胞术评估血液和FNAs中b细胞的类别转换。结果服用SCIT后，AR症状、药物使用和嗜碱性粒细胞对过敏原的敏感性均有所降低。有趣的是，SCIT增加后，血浆中过敏原特异性IgA、IgG和IgG4水平升高，而NAL中过敏原特异性IgE和IgA水平在此时间点下降。此外，这些结果还伴随着血液和淋巴结中常规（IgD - CD27+）和非常规（IgD - CD27−）记忆B细胞的增加。结论：本研究强调了SCIT对局部和全身免疫的不同影响，并确定了与治疗相关的早期免疫变化。然而，确认长期耐受性需要延长随访时间，包括季节分析。NAL中过敏原特异性IgA的局部减少，以及过敏原特异性IgA和IgG4的全身性增加，强调了在评估SCIT疗效时评估粘膜和全身反应的重要性。

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来源期刊

Clinical and Translational Allergy Immunology and Microbiology-Immunology

CiteScore

7.50

自引率

4.50%

发文量

117

审稿时长

12 weeks

期刊介绍： Clinical and Translational Allergy, one of several journals in the portfolio of the European Academy of Allergy and Clinical Immunology, provides a platform for the dissemination of allergy research and reviews, as well as EAACI position papers, task force reports and guidelines, amongst an international scientific audience. Clinical and Translational Allergy accepts clinical and translational research in the following areas and other related topics: asthma, rhinitis, rhinosinusitis, drug hypersensitivity, allergic conjunctivitis, allergic skin diseases, atopic eczema, urticaria, angioedema, venom hypersensitivity, anaphylaxis, food allergy, immunotherapy, immune modulators and biologics, animal models of allergic disease, immune mechanisms, or any other topic related to allergic disease.