Allergen immunotherapy and dupilumab in atopic dermatitis: Clinical efficacy and disparities in immunological indicators

IF 3.9 2区 医学 Q2 ALLERGY
Jin Liu MM , Lin Yang MD, PhD , Qingxiu Xu MD , Qing Jiang PhD , Nan Huang MD , Wenjing Li PhD , Yaqi Yang MD , Dongxia Ma MD , Le Li MM , Yangxue Fu PhD , Hao Chen PhD , Rongfei Zhu MD, PhD
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Abstract

Objective

Allergen immunotherapy (AIT) and dupilumab have been confirmed to improve symptoms of atopic dermatitis (AD); however, the precise immune mechanisms underlying their efficacy and whether they can elicit synergistic immune effects remain not fully elucidated. We aimed to investigate the clinical efficacy and immunological changes in AD patients undergoing AIT, dupilumab, and a combination of AIT and dupilumab treatment.

Methods

Clinical data, serum samples, and peripheral blood mononuclear cells (PBMC) were collected from house dust mite (HDM)-sensitized AD patients receiving AIT and/or dupilumab at baseline and 6 months. Changes in clinical efficacy, HDM-specific IgE and IgG4, serum cytokines, and lymphocyte subgroups were compared among the treatment groups.

Results

A total of 77 AD patients were included, with 39 in the AIT group, 19 in the dupilumab group, and 19 in the AIT combined dupilumab group. The SCORAD scores significantly improved in all groups after 6 months. Levels of HDM-specific IgE and total IgE remained stable in the AIT group but decreased in the dupilumab and combination groups. Levels of IgG4 against major mite components Der p1 and Der p23 increased in the AIT group and combined treatment group. Serum cytokine levels showed no significant changes, except for a decrease in CCL17 in the dupilumab group. Th1/Th2 and Th17/Th2 ratios increased after dupilumab treatment. There were notable differences in T cell subpopulations when PBMCs were stimulated with HDM extracts after 6-month treatment, tSNE analysis showed the proportion of IL-4+IL-13+CRTH2+T cells increased in the dupilumab group but had no changes in the AIT and combination group.

Conclusions

AIT, dupilumab, and their combination improved clinical symptoms and quality of life in AD patients. AIT promoted allergen-specific IgG4 production, while dupilumab modulated T cell responses and reduced allergen-specific IgE synthesis. The combination of AIT and dupilumab exhibited the immunological parameter changes characteristic of both treatments but did not result in a significantly greater improvement in AD symptoms.
过敏原免疫疗法和杜匹单抗治疗特应性皮炎:临床疗效和免疫学指标的差异
目的:证实过敏原免疫疗法(AIT)和杜匹单抗(dupilumab)可改善特应性皮炎(AD)的症状;然而,其疗效背后的确切免疫机制以及它们是否能引起协同免疫效应仍未完全阐明。我们的目的是研究接受AIT和dupilumab以及AIT和dupilumab联合治疗的AD患者的临床疗效和免疫学变化。方法收集屋尘螨(HDM)致敏AD患者在基线和6个月时接受AIT和/或dupilumab治疗的临床资料、血清和外周血单核细胞(PBMC)。比较两组患者临床疗效、hdm特异性IgE、IgG4、血清细胞因子、淋巴细胞亚群的变化。结果共纳入77例AD患者,其中AIT组39例,dupilumab组19例,AIT联合dupilumab组19例。6个月后各组患者的SCORAD评分均有显著提高。hdm特异性IgE和总IgE水平在AIT组保持稳定,但在dupilumab和联合用药组下降。抗螨主要成分Der p1和Der p23的IgG4水平在AIT组和联合治疗组均升高。除了dupilumab组CCL17降低外,血清细胞因子水平无显著变化。dupilumab治疗后Th1/Th2和Th17/Th2比值升高。治疗6个月后,HDM提取物刺激PBMCs时,T细胞亚群有显著差异,tSNE分析显示,杜匹单抗组IL-4+IL-13+CRTH2+T细胞比例增加,而AIT和联合用药组没有变化。结论sait、dupilumab及其联合治疗可改善AD患者的临床症状和生活质量。AIT促进过敏原特异性IgG4的产生,而dupilumab调节T细胞反应并降低过敏原特异性IgE合成。联合使用AIT和dupilumab表现出两种治疗所特有的免疫参数变化,但并未导致AD症状的显著改善。
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来源期刊
World Allergy Organization Journal
World Allergy Organization Journal Immunology and Microbiology-Immunology
CiteScore
9.10
自引率
5.90%
发文量
91
审稿时长
9 weeks
期刊介绍: The official pubication of the World Allergy Organization, the World Allergy Organization Journal (WAOjournal) publishes original mechanistic, translational, and clinical research on the topics of allergy, asthma, anaphylaxis, and clincial immunology, as well as reviews, guidelines, and position papers that contribute to the improvement of patient care. WAOjournal publishes research on the growth of allergy prevalence within the scope of single countries, country comparisons, and practical global issues and regulations, or threats to the allergy specialty. The Journal invites the submissions of all authors interested in publishing on current global problems in allergy, asthma, anaphylaxis, and immunology. Of particular interest are the immunological consequences of climate change and the subsequent systematic transformations in food habits and their consequences for the allergy/immunology discipline.
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