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在接受抗 IL-4Rα 单克隆抗体或过敏原特异性免疫治疗的伴有变应性鼻结膜炎的特应性皮炎患者中,过敏原特异性嗜碱性粒细胞活化和 T 细胞增殖的差异。

Differences in allergen-specific basophil activation and T cell proliferation in atopic dermatitis patients with comorbid allergic rhinoconjunctivitis treated with a monoclonal anti-IL-4Rα antibody or allergen-specific immunotherapy.

机构信息

Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.

出版信息

Immun Inflamm Dis. 2023 Apr;11(4):e808. doi: 10.1002/iid3.808.

Abstract

BACKGROUND

Atopic dermatitis (AD), a chronic inflammatory disorder, is often accompanied by allergic rhinoconjunctivitis (ARC) as a co-morbidity. The use of a monoclonal anti-IL-4Rα antibody has been effective in controlling moderate to severe AD symptoms. Allergen-specific immunotherapy (AIT) is widely used for the treatment of ARC and asthma. The effects of AIT on basophil reactivity/effector functions have already been examined and used as indicators of the treatment efficacy. However, it is unclear, how an anti-IL-4Rα antibody can influence allergen-specific immune responses of basophils and T cells of AD patients with comorbid ARC.

OBJECTIVE

To investigate the effect of a monoclonal anti-IL-4Rα antibody on the in vitro allergic responses of basophils and T cells deriving from AD patients with comorbid ARC.

METHODS

Blood samples of 32 AD patients were obtained before, after 4 and 16 weeks of an anti-IL-4Rα antibody therapy (300 mg subcutaneously/2 weeks; n = 21) or AIT (daily sublingual application; n = 11). Patients treated with an anti-IL-4Rα antibody were grouped according to their serum specific immunoglobulin E levels and ARC symptoms, while patients receiving an AIT were additionally grouped according to the allergen specificity of their AIT. Basophil activation test and T cell proliferation assays were undertaken after an in vitro allergen stimulation.

RESULTS

A significant reduction of the immunoglobulin E levels and the allergen-specific T cell proliferation was observed in AD patients treated with an anti-IL-4Rα -antibody, while the allergen-specific basophil activation/sensitivity were found to be significantly increased. In patients receiving an AIT, the in vitro allergen-specific basophil activation and the T cell proliferation were found to be significantly decreased in response to seasonal allergens.

CONCLUSIONS

An IL-4Rα blockade induced by a monoclonal anti-IL-4Rα antibody leads to an increased activity/sensitivity of early effector cells (such as basophils), in contrast to a decreasing reactivity observed under an AIT. The late-phase T cell reaction to allergens did not differ between the herein assessed treatments.

摘要

背景

特应性皮炎(AD)是一种慢性炎症性疾病,常伴有变应性鼻结膜炎(ARC)等合并症。使用单克隆抗 IL-4Rα 抗体已被证明能有效控制中重度 AD 症状。变应原特异性免疫疗法(AIT)广泛用于治疗 ARC 和哮喘。AIT 对嗜碱性粒细胞反应/效应功能的影响已被研究,并作为治疗效果的指标。然而,尚不清楚抗 IL-4Rα 抗体如何影响伴有 ARC 的 AD 患者的嗜碱性粒细胞和 T 细胞的变应原特异性免疫反应。

目的

研究单克隆抗 IL-4Rα 抗体对伴有 ARC 的 AD 患者的嗜碱性粒细胞和 T 细胞体外变应原反应的影响。

方法

在接受抗 IL-4Rα 抗体治疗(300mg 皮下/2 周;n=21)或 AIT(每日舌下应用;n=11)前、治疗 4 周和 16 周后,从 32 名 AD 患者中采集血液样本。接受抗 IL-4Rα 抗体治疗的患者根据其血清特异性 IgE 水平和 ARC 症状进行分组,而接受 AIT 的患者则根据其 AIT 的过敏原特异性进行分组。在体外过敏原刺激后进行嗜碱性粒细胞激活试验和 T 细胞增殖试验。

结果

抗 IL-4Rα 抗体治疗的 AD 患者的 IgE 水平和过敏原特异性 T 细胞增殖显著降低,而过敏原特异性嗜碱性粒细胞激活/敏感性显著增加。在接受 AIT 的患者中,季节性过敏原刺激后体外过敏原特异性嗜碱性粒细胞激活和 T 细胞增殖显著降低。

结论

单克隆抗 IL-4Rα 抗体诱导的 IL-4Rα 阻断导致早期效应细胞(如嗜碱性粒细胞)的活性/敏感性增加,而 AIT 观察到的反应性降低。在此评估的治疗方法中,过敏原的晚期 T 细胞反应没有差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bbd3/10091378/e21c386709b3/IID3-11-e808-g002.jpg

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