The Unit of Proteomics and Flow Cytometry, Division of Allergy and Clinical Immunology, Technion, Haifa, Israel.
Department of Pathology-Bnai-Zion Medical Center, Faculty of Medicine, Technion, Haifa, Israel.
Clin Exp Allergy. 2020 Jul;50(7):799-804. doi: 10.1111/cea.13616.
Chronic spontaneous urticaria (CSU) is considered an autoimmune disorder in 50% of cases at least, in which T- and mast cell mediators are considered to be the primary cause of symptoms. However, H -antihistamines, cyclosporine A, and omalizumab fail to achieve complete symptom amelioration in up to 70% of patients. This suggests that other inflammatory pathways are involved and that additional and more effective treatments need to be developed.
This preliminary report examines the possibility that interleukin-17 (IL-17), a cytokine involved in the pathogenesis of many autoimmune diseases, may contribute to CSU and its inhibition may offer a relevant therapeutic target.
The expression of IL-17A in skin biopsies of 20 CSU patients and 10 healthy controls was determined by quantitative histomorphometry. We also assessed the response to secukinumab (anti-IL-17A) treatment patients of eight severe CSU (7-day urticaria activity score UAS7 32-40) who were H -antihistamine and omalizumab-resistant.
Increased numbers of CD4+ T cells and mast cells were present in both lesional and non-lesional skin of CSU patients compared with healthy controls. Both types of cells were strongly positive for IL-17A and found to be in close proximity to each other. All eight patients treated with the anti-IL-17A antibody, secukinumab, showed significant improvement in CSU disease activity. The action of secukinumab was shown to be relatively slow in onset. The significant reduction in disease activity from baseline UAS7 was demonstrated to be 55% and 82% at 30 and 90 days, respectively.
These findings suggest that IL-17 is involved in the pathogenesis of CSU and that IL-17 should be investigated as a therapeutic target in future studies with larger numbers of patients.
慢性自发性荨麻疹（CSU）至少有 50%的病例被认为是自身免疫性疾病，其中 T 细胞和肥大细胞介质被认为是症状的主要原因。然而，H1 抗组胺药、环孢素 A 和奥马珠单抗在多达 70%的患者中无法实现完全缓解症状。这表明其他炎症途径也参与其中，需要开发其他更有效的治疗方法。
本初步报告探讨了白细胞介素-17（IL-17）作为一种参与许多自身免疫性疾病发病机制的细胞因子，是否可能导致 CSU 的发生，其抑制作用是否可能成为一个相关的治疗靶点。
通过定量组织形态计量学，检测 20 例 CSU 患者和 10 例健康对照者皮肤活检组织中 IL-17A 的表达。我们还评估了抗 IL-17A 治疗 8 例重度 CSU 患者（7 天荨麻疹活动评分 UAS7 32-40）的反应，这些患者对 H1 抗组胺药和奥马珠单抗耐药。
与健康对照组相比，CSU 患者的皮损和非皮损皮肤中均存在数量增加的 CD4+T 细胞和肥大细胞。这两种细胞均对 IL-17A 呈强阳性，且彼此靠近。接受抗 IL-17A 抗体 secukinumab 治疗的所有 8 例患者的 CSU 疾病活动均有显著改善。secukinumab 的作用起效相对较慢。基线 UAS7 时的疾病活动显著降低，分别在 30 天和 90 天时达到 55%和 82%。
这些发现表明，IL-17 参与了 CSU 的发病机制，IL-17 应作为未来研究的治疗靶点，纳入更多患者进行研究。
