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, namely Type I autoallergic CSU, which is mediated by IgE autoantibodies against autoallergens and Type IIb autoimmune CSU (aiCSU) mediated by IgG autoantibodies against IgE and its high affinity 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 (IgG-anti-FcεRI/IgE), 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(TPO) 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 strongly linked to the features of Type IIb aiCSU such as basophil activation test (BAT) positivity, ASST positivity, basopenia, eosinopenia and poor response to antihistamine treatment. Both parameters are easy-to-assess and cost-effective and can be 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 can be an important tool for further research on this disease, for clinical trials and programs of novel treatment options, and for developing a cure. 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 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.

Project Lead: Yikui Xiang, Pavel Kolkhir

Project Advisor: Marcus Maurer

Steering Committee: Simon Francis Thomsen, Luis Felipe Chiaverini Ensina, Ana Gimenez-Arnau, Ivan Cherrez, Kanokvalai Kulthanan, Désirée Larenas-Linnemann

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 information collected prospectively how these patients are treated, so that we can investigate possible links between markers and response to treatment.

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) and exchanging ideas in UCARE network.

We are now making the final preparations before the launch of the study and will invite all UCAREs to participate soon.

Contact:

Dr. Yikui Xiang: yi-kui.xiangATcharite.de

Dr. Pavel Kolkhir: pavel.kolkhirATcharite.de

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