变应性鼻炎的皮下变应原特异性免疫疗法:鼻黏膜和血液中不同的IgA反应以及淋巴结和血液中B细胞类别转换的验证
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.
作者信息
Jafari Maryam, Petro Marianne, Paziou Eirini, Hjalmarsson Eric, Karlsson Agnetha, Ezerskyte Monika, Hellkvist Laila, Georén Susanna Kumlien, Cardenas Eduardo I, Cardell Lars-Olaf
机构信息
Division of Ear, Nose, and Throat Diseases, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Department of Otorhinolaryngology, Karolinska University Hospital, Stockholm, Sweden.
出版信息
Clin Transl Allergy. 2025 Sep;15(9):e70097. doi: 10.1002/clt2.70097.
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 (IgDCD27) and unconventional (IgDCD27) 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.
背景
皮下免疫疗法(SCIT)作为变应性鼻炎(AR)的基础治疗方法已有50多年历史,一直显示出能减轻症状并调节免疫反应。尽管如此,SCIT疗效的潜在机制仍未完全明确,尤其是在淋巴结和鼻黏膜中的局部免疫反应方面。
目的
确定SCIT治疗对血液和鼻黏膜中免疫球蛋白产生以及血液和淋巴结中B细胞类别转换的影响。
方法
收集23例桦树和/或梯牧草花粉诱导的AR患者在SCIT剂量增加前后的血液、鼻腔灌洗液(NAL)和腹股沟淋巴结细针抽吸物(FNA)。通过症状和药物评分以及变应原介导的嗜碱性粒细胞活化来评估对SCIT的总体反应。通过ELISA法检测血液和NAL中的变应原特异性IgE、IgA、IgG和IgG4。通过流式细胞术评估血液和FNA中的B细胞类别转换。
结果
SCIT剂量增加后,AR症状、药物使用以及嗜碱性粒细胞对变应原的敏感性降低。有趣的是,SCIT剂量增加后,变应原特异性IgA、IgG和IgG4的血浆水平升高,而此时NAL中变应原特异性IgE和IgA水平降低。此外,这些结果伴随着血液和淋巴结中传统(IgD⁺CD27⁻)和非传统(IgD⁻CD27⁺)记忆B细胞的增加。
结论
本研究突出了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,要确认长期耐受性需要延长随访时间,包括季节内分析。NAL中变应原特异性IgA的局部降低以及变应原特异性IgA和IgG4的全身增加,强调了在评估SCIT疗效时同时评估黏膜和全身反应的重要性。
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