Characterization of the Prevalence, Immunologic Features, and Clinical Implications of Autoimmune Subtypes of Chronic Spontaneous Urticaria (CAS-CSU)

慢性自发性荨麻疹 (CAS-CSU) 自身免疫亚型的患病率、免疫学特征和临床意义的表征

• 批准号: 464568473
• 负责人: Professor Dr. Marcus Maurer
• 金额: --
• 依托单位: Institut für Allergieforschung (IFA)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/464568473?language=en
• 关键词: Characterization; Prevalence; Immunologic; Features; Clinical

Chronic spontaneous urticaria (CSU) is a common autoimmune disease, but its pathomechanisms remain to be clarified in detail. Importantly, the two known autoimmune endotypes of CSU remain ill-characterized and can currently not be diagnosed in routine clinical practice. This project will change this. We will characterize, in detail, Type I and Type IIb autoimmune CSU, determine the prevalence of these two endotypes, and identify their immunological and clinical features. This is now possible, as we have developed suitable assays such as ELISA assays for IgE directed to common autoantigens, peptide arrays for relevant IgE autoantibodies, a total auto-IgE assay, and a novel mast cell histamine release assay. We also had to put together suitable cohorts of well-characterized CSU patients, which was completed mid-2020. Thus, we are now ready to start this project and will, over the course of the next three years, address our overall hypothesis: Type I autoimmune (autoallergic) and Type IIb autoimmune CSU are major and distinct disease subtypes. Specifically, we will determine, in Aim 1, the prevalence of Type I autoimmunity in patients with CSU as well as the immunological and clinical profiles of patients with this CSU subtype. In Aim 2, we will assess the prevalence of Type IIb autoimmunity in patients with CSU and identify its immunological and clinical features. Aim 3 will compare Type I and Type IIb autoimmune CSU patients both immunologically and clinically. We expect that this project will provide validation of the immunological assays developed, information on the prevalence of autoimmune CSU endotypes, and endotype-specific profiles and characterization, both immunologically and clinically. These results will help to clarify the mechanisms of CSU and may also provide insights on drivers of the pathogenesis of chronic inducible urticaria as well as other mast cell-driven diseases.

慢性自发性荨麻疹(CSU)是一种常见的自身免疫性疾病，其发病机制尚不清楚。重要的是，已知的两种CSU自身免疫内型仍不明确，目前尚不能在常规临床实践中诊断。这个项目将改变这一点。我们将详细描述I型和IIb型自身免疫性CSU的特征，确定这两种内型的患病率，并确定它们的免疫学和临床特征。现在，这是可能的，因为我们已经开发出合适的分析方法，例如针对常见自身抗原的IgE的ELISA分析，相关的IgE自身抗体的多肽阵列，总的自身IgE分析，以及一种新的肥大细胞组胺释放分析。我们还必须组织合适的CSU患者队列，这项工作已于2020年年中完成。因此，我们现在准备开始这个项目，并将在未来三年的过程中，解决我们的总体假设：I型自身免疫(自身过敏)和IIb型自身免疫性CSU是主要的和不同的疾病亚型。具体地说，在目标1中，我们将确定CSU患者中I型自身免疫的患病率，以及该CSU亚型患者的免疫学和临床特征。在目标2中，我们将评估IIb型自身免疫在CSU患者中的患病率，并确定其免疫学和临床特征。目的3将从免疫学和临床两方面比较I型和IIb型自身免疫性CSU患者。我们期望这个项目将提供所开发的免疫学分析的验证，关于自身免疫性CSU内型流行的信息，以及免疫和临床上的内型特异性图谱和特征。这些结果将有助于阐明CSU的机制，也可能为慢性诱导性荨麻疹和其他肥大细胞驱动的疾病的发病机制提供深入的认识。