No abstract

Introduction Benralizumab is a monoclonal antibody that binds the α subunit of the receptor to IL-5. As IL-5 is implicated in disease states that are mediated by eosinophils, benralizumab is an attractive option for use in the management of asthma. As a result of enhanced antibody-directed cell cytotoxicity, it has enhanced eosinophil-depleting activity as compared with neutralizing monoclonal antibody directed against IL-5. Areas covered This review presents the available data on benralizumab, including pharmacodynamics, pharmacokinetics, preclinical data and relevant clinical studies. Expert opinion Our review indicates that although further investigation is necessary to demonstrate clinical benefit, benralizumab remains a promising treatment modality.

Background The prevalence of food allergy has steadily increased, especially in children. Reflux disease, a very common problem in children, is often treated with gastric acid suppressive (GAS) medications which may alter the processing of food allergens, thereby affecting oral mucosal tolerance. Objective The purpose of this study was to determine if use of GAS medications is associated with the occurrence of food allergies in children. Methods: Using a large national commercial insurance database, we identified 4724 children aged 0–18 years who were diagnosed with Gastroesophageal Reflux Disease (GERD) and treated with either GAS medications between (1/1/2008 and 9/30/2009). We then matched 4724 children with GERD not treated with GAS medications and 4724 children without GERD and not treated with GAS medications, at a 1 to 1 ratio, on age, gender and number of atopic risk factors. Patients were followed for 12 months. Results In comparison to the referent (children without GERD who received no GAS medications), children with GERD who were treated with GAS were more likely to be diagnosed with a food allergy (Hazard ratio (HR): 3.67, 95% CI 2.15–6.27), as were children with GERD diagnosis but who were not treated with GAS medications (HR: 2.15, 95% CI: 1.21–3.81),. A direct comparison of the two GERD cohorts showed that children with GERD who were treated with GAS had a greater risk of food allergy than those with GERD who were untreated (HR, 1.68, 95%CI, 1.15–2.46). Conclusion Treatment with GAS medications is associated with the occurrence of food allergy, an effect not apparently related to a diagnosis of GERD alone.

Background Th2 cells play a critical role in the pathogenesis of allergic asthma. Established Th2 cells have been shown to resist reprogramming into Th1 cells. The inherent stability of Th2 cells poses a significant barrier to treating allergic diseases. Objective We sought to understand the mechanisms by which CD4+ T cells from asthmatic patients resist the IL-27-mediated inhibition. Methods We isolated and cultured CD4+ T cells from both healthy individuals and allergic asthmatic patients in order to test whether IL-27 can inhibit IL-4 production by the cultured CD4+ T cells using ELISA. Culturing conditions that resulted in resistance to IL-27 were determined using both murine and human CD4+ T cell culture systems. STAT1 phosphorylation was analyzed by Western blot and flow cytometry. Suppressor of cytokine signaling (Socs) mRNA expression was measured by quantitative PCR. The small interfering RNA method was used to knockdown the expression of Socs3 mRNA. Main Results We demonstrated that CD4+ T cells from asthmatic patients resisted the suppression of IL-4 production mediated by IL-27. We observed that repeated exposure to Th2-inducing conditions rendered healthy human CD4+ T cells resistant to IL-27-mediated inhibition. Using an in vitro murine culture system, we further demonstrated that repeated or higher doses of IL-4 stimulation, but not IL-2 stimulation, upregulated Socs3 mRNA expression and impaired IL-27-induced STAT1 phosphorylation. The Knockdown of Socs3 mRNA expression restored IL-27-induced STAT1 phosphorylation and IL-27-mediated inhibition of IL-4-production. Conclusions Our findings demonstrate that differentiated Th2 cells can resist IL-27-induced reprogramming toward Th1 cells by downregulating STAT1 phosphorylation and likely explain why the CD4+ T cells of asthmatic patients are resistant to IL-27-mediated inhibition.