Department of Dermatology and Allergy, University Hospital Bonn, Bonn, Germany.
Immun Inflamm Dis. 2023 Apr;11(4):e808. doi: 10.1002/iid3.808.
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.
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.
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.
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.
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.
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。
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。
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。
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。
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。