Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria
Functional and phenotypic analysis of basophils allows determining distinct subtypes in patients with chronic urticaria
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DOI：
10.1111/all.13215
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发表时间：
2017-12-01
期刊：
影响因子：
12.4
通讯作者：
Pfuetzner, W.
中科院分区：
文献类型：
--
作者：
Rauber, M. M.;Pickert, J.;Pfuetzner, W.
慢性荨麻疹（chronic urticaria，CU）是一种常见的以反复发作的荨麻疹为特征的皮肤病.虽然临床症状是由于皮肤肥大细胞释放组胺引起的，但其潜在的病理生理机制仍不清楚。然而，以前的研究表明，嗜碱性粒细胞可能是相关的。此外，抗IgE或其受体Fc β RI的自身抗体的出现，方法采用嗜碱性粒细胞活化试验检测60例CU患者外周血嗜碱性粒细胞对特异性抗Fc抗体抑制剂和IgE非依赖性fMLP刺激的反应性，并与IgE-Fc抗体阳性的CU患者进行比较。介导的过敏性鼻炎（n=10）和健康对照（n=10）。此外，在嗜碱性粒细胞上定量免疫球蛋白受体（Fc ε RI、FcRII）表达和表面结合抗体（IgE、IgG）。此外，CU血清的自身反应能力进行了评估和荨麻疹相关症状进行了评估，UCT和CU-Q（2）oL. ResultsScreening刺激CU患者的嗜碱性粒细胞通过Fc γ RI，我们确定了三种不同的免疫表型。一个患者的嗜碱性粒细胞亚群对Fc ε RI刺激有反应，而其他患者的嗜碱性粒细胞抗Fc ε RI无反应。在后者中，确定了一个具有明显的碱减少症的亚组。值得注意的是，这一组的特点是增强血清诱导的嗜碱性粒细胞活化，甲状腺过氧化物酶的自身抗体水平增加，也表现出最强的疾病对他们的生活quality.ConclusionsPatients with CU可以分为三个免疫亚组的基础上，他们的嗜碱性粒细胞的反应性和频率。这些表型与不同的临床特征相关，表明嗜碱性粒细胞在CU病理生理学中起重要作用。
BackgroundChronic urticaria (CU) is a frequent skin disease characterized by relapsing appearance of pruritic hives. While clinical symptoms are due to the release of histamine by cutaneous mast cells, the underlying pathophysiology is still unknown. However, previous studies indicate that basophils might be of relevance. Besides, the occurrence of autoantibodies against IgE or its receptor, Fc epsilon RI, and the therapeutic efficacy of anti-IgE antibodies imply that IgE-mediated mechanisms also play an important role in CU.MethodsReactivity of CU patients' peripheral blood basophils (n=60) to specific anti-Fc epsilon RI and IgE-independent fMLP stimulation was determined by basophil activation test in comparison with patients suffering from IgE-mediated allergic rhinitis (n=10) and healthy controls (n=10). In addition, immunoglobulin receptor (Fc epsilon RI, FcRII) expression and surface bound antibodies (IgE, IgG) were quantified on basophils. Furthermore, the autoreactive capacity of CU sera was evaluated and urticaria-related symptoms were assessed by both UCT and CU-Q(2)oL.ResultsStimulating CU patients' basophils via Fc epsilon RI, we identified three distinct immunologic phenotypes. One subgroup of patients' basophils reacted to Fc epsilon RI stimulation, whereas the others had anti-Fc epsilon RI nonreactive basophils. Among the latter, a subgroup with pronounced basopenia was identified. Of note, this group was characterized by augmented serum-induced basophil activation, increased levels of autoantibodies against thyroid peroxidase, and also exhibited the strongest disease impact on their quality of life.ConclusionsPatients with CU can be categorized into three immunologic subgroups based on their basophil reactivity and frequency. These phenotypes are associated with different clinical characteristics, pointing to basophils as important players in CU pathophysiology.