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

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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.