Urticaria is a condition that has a lifetime likelihood of 25% in the United States and a significant proportion of these individuals will experience the disease in a cyclical form that lasts 1-10 years and for which no cause can be identified. If this condition occurs, the patient is given the diagnosis of chronic idiopathic urticaria (CIU). Theof condition can be severe and produce a reduction in the quality of life similar to that measured for heart diseases. At present, there is no known mechanism but recent studies have shown that the disease can be treated with non-aggregating, anti-IgE antibody (omalizumab). More remarkably, treatment with omalizumab leads to remission of active disease with a rapidity that is not consistent with expectations for changes in skin mast cells. There are numerous indications that basophils play a role in expression of this disease and the rate of clinical improvement on omalizumab is consistent with the timing of basophils changes seen in studies of allergic subjects during treatment with omalizumab. This proposal will directly test the hypothesis that changes in IgE-dependent functionality of basophils will be concordant with the rate of clinical improvement during treatment with omalizumab. This study will conduct a clinical trial of omalizumab therapy for patients with active CIU. This trial will be characterized by a hig temporal frequency of both clinical assessments and a variety of metrics of basophil and mast cell function.
IgE receptor activation of mast cells and basophils is involved in allergic reactions that feature hives, but in the case of chronic hives, there is no obvious trigger and the pathogenesis is unclear. Recently, a new therapy targeting IgE (omalizumab) has led to rapid and remarkable improvement of symptoms in chronic hive patients, supporting a role for IgE in this disease. In this proposal, we will perform a clinical tial with omalizumab in chronic hives to test whether the rapid clinical improvement occurs concurrently with changes in IgE receptors on basophils or mast cells.
|Saini, Sarbjit S; Kaplan, Allen P (2018) Chronic Spontaneous Urticaria: The Devil's Itch. J Allergy Clin Immunol Pract 6:1097-1106|
|MacGlashan, Donald (2018) Auto-antibodies to IgE and FceRI and the Natural Variability of SYK Expression in Basophils. J Allergy Clin Immunol :|
|Straesser, Matthew D; Oliver, Eric; Palacios, Thamiris et al. (2018) Serum IgE as an immunological marker to predict response to omalizumab treatment in symptomatic chronic urticaria. J Allergy Clin Immunol Pract 6:1386-1388.e1|
|Kaplan, A P; Giménez-Arnau, A M; Saini, S S (2017) Mechanisms of action that contribute to efficacy of omalizumab in chronic spontaneous urticaria. Allergy 72:519-533|
|Doong, Judy C; Chichester, Kris; Oliver, Eric T et al. (2017) Chronic Idiopathic Urticaria: Systemic Complaints and Their Relationship with Disease and Immune Measures. J Allergy Clin Immunol Pract 5:1314-1318|