Suppression of Basophil FcεRI Activation by Serum from Active Chronic Idiopathic/Spontaneous Urticaria (CIU/CSU) Subjects

Chronic idiopathic/spontaneous urticaria (CIU/CSU), which affects ~1% of the United States population, is defined as recurrent hives for >6 weeks (Kaplan and Greaves, 2009). Active CIU/CSU patients uniquely display suppressed basophil FcεRI-mediated histamine release (BHR) (Saini, 2014). This is a feature that improves in disease remission (Eckman et al., 2008; Kern and Lichtenstein, 1976; Oliver, 2014). The pathways leading to basophil FcεRI suppression in CIU/CSU are unclear. There is evidence that IgE plays a role in urticaria. For example, injection of cold urticaria patients’ serum into a healthy subject’s skin transfers the sensitivity to the cold stimulus (Gruber et al., 1988). Clinical trials with monoclonal anti-IgE (omalizumab) in subjects with CIU/CSU have shown rapid symptom relief, which implicates IgE in the disease pathway (Gober et al., 2008; Maurer et al., 2013; Saini et al., 2011). Furthermore, the autoimmune theory of CIU/CSU pathogenesis proposes that serum IgG autoantibodies specific to IgE or the IgE receptor directly activate skin mast cells and basophils in a subset of CIU/CSU subjects (Kaplan and Greaves, 2009). In this study, we examined the ability of active CIU/CSU patients’ serum to transfer FcεRImediated BHR suppression to healthy basophils and further test the contributions of IgE, IgG, and complement in the observed basophil mediator suppression.