Dear UCARE friends and colleagues,

We are launching a new project, which is called CU-TIGER, The Characterization of urticaria markers including anti-TPO and IgE in serum.

𝗕𝗮𝗰𝗸𝗴𝗿𝗼𝘂𝗻𝗱/ 𝗿𝗮𝘁𝗶𝗼𝗻𝗮𝗹𝗲
Two endotypes of chronic spontaneous urticaria (CSU) have been recently described, ie Type I autoimmune CSU (aiCSU), which is also called autoallergic CSU and mediated by IgE autoantibodies and Type IIb aiCSU mediated by antibodies against IgE and its receptor, FcεRI. Type IIb aiCSU is characterized by high disease activity, high rates of autoimmune comorbidity, and poor response to treatment with antihistamines and omalizumab. Tests for Type IIb aiCSU, i.e. the autologous serum skin test (ASST), autoantibody immunoassays, and basophil testing, are not widely available and have limitations, e.g. some are invasive, not sufficiently validated and/or cost intensive. The availability of simple, valid and reliable biomarkers for Type IIb aiCSU would improve routine clinical care by guiding a personalized approach to CSU management including the prediction of its clinical course and response to treatment.

Recently, elevated levels of IgG-anti-thyroid peroxidase and low levels of total IgE were reported to be common in Type IIb aiCSU. The combination of low total IgE and high IgG-anti-TPO is linked to the features of Type IIb aiCSU such as basophil activation test (BAT) positivity, ASST positivity, basopenia and eosinopenia and poor response to antihistamine treatment. Both parameters are easy-to-assess and cost-effective and are routinely done in many healthcare settings. The revised international urticaria guideline recommends IgE and IgG-anti-TPO as routine diagnostic measures in CSU patients in specialized care.

Importantly, the use of the combination of these parameters can improve the stratification of patients into aiCSU and non-aiCSU. It might be a good marker for identifying patients for participation in clinical trials with Type IIb aiCSU-targeted treatment. Furthermore, this combination may be of use for the identification of patients at risk for autoimmune thyroiditis/hypothyroidism and other autoimmune diseases.

As of now, large multicenter studies on IgE and anti-TPO as markers of Type IIb aiCSU are missing. CU-TIGER will change this.

𝗔𝗶𝗺𝘀
In this project we will investigate/characterize:
1. how many IgE-low and IgG-anti-TPO-high CSU patients have functional autoantibodies (IgG, IgM and/or IgE) assessed by both BAT and immunoassays;
2. appropriate cut-off values;
3. whether an additional parameter, e.g. basopenia, would increase diagnostic accuracy of using TPO/IgE for diagnosis of aiCSU;
4. patients who have low IgE, high anti-TPO, both, or none for their clinical characteristics;
5. link between IgE/anti-TPO and treatment responses, at least responses to antihistamine treatment (standard and higher than standard dosed treatment) and omalizumab.

𝗛𝗼𝘄 𝘆𝗼𝘂 𝗰𝗮𝗻 𝗵𝗲𝗹𝗽
To accomplish these aims we will analyse sera of as many CSU patients as possible treated at UCAREs. That's where you come in. Send us serum samples of your patients, which we will then analyse (for free) here at the Berlin UCARE. We will measure total IgE and TPO antibodies as well as additional autoimmunity-related parameters. Please also provide basic clinical information for these patients, so that we can investigate possible links.

𝗖𝗼𝗮𝘂𝘁𝗵𝗼𝗿𝘀𝗵𝗶𝗽
As for all UCARE projects, we will publish the results together. UCAREs who provide 10 serum samples (with matching clinical data) get to nominate one coauthor for each CU-TIGER publication. Twenty additional sera (and matching data) will give you a second authorship. If you provide 60 or more sera (and matching) data, you get to nominate 3 authors from your UCARE. All coauthors have to meet ICMJE requirements, i.e. actively contribute to the development of the manuscript(s).

Today, all we need from you is to know if you are interested in taking part in CU-TIGER. Please complete this short survey by the 31st of March.