Kinetics of mast cell, basophil, and oral food challenge responses in omalizumab-treated adults with peanut allergy
ABSTRACT BACKGROUND: Monoclonal antibodies directed at IgE demonstrate clinical efficacy in subjects with peanut allergy, but previous studies have not addressed the kinetics of the clinical response or the role of mast cells and basophils in the food-induced allergic response. OBJECTIVE: We sought to determine the kinetics of the clinical response to omalizumab and whether clinical improvement is associated with either mast cell or basophil suppression. METHODS: Subjects with peanut allergy were treated with omalizumab for 6 months and assessed for clinical and cellular responses. At baseline, subjects had a double-blind, placebo-controlled oral food challenge (OFC), skin prick test titration (SPTT), and basophil histamine release (BHR) to peanut. BHR was repeated at week 2 and then weekly until it decreased to less than 20% of baseline values. The OFCs and SPTTs were repeated after the BHR reduction (or at week 8 if BHR did not decrease) and again at 6 months. RESULTS: Fourteen subjects enrolled in the study. At the second food challenge, there was a significant increase in the threshold dose of peanut inducing allergic symptoms (80 to 6500 mg, P < .01). Peanut-induced BHR was either completely suppressed (n = 5) or 10-fold more allergen was required to induce maximal BHR (n = 9), and SPTT responses were not significantly changed from baseline. After 6 months of omalizumab, further changes in the OFC threshold dose or BHR were not observed, but a significant suppression in SPTTs was identified. CONCLUSIONS: The clinical response to omalizumab occurs early in treatment when the basophil, but not the mast cell, is suppressed, supporting a role for the basophil in acute food reactions.
[Show abstract] [Hide abstract]
ABSTRACT: Food allergy is a major public health problem without satisfactory treatment options. Of several new treatments being studied, oral immunotherapy (OIT) appears to be the most promising. Unfortunately, OIT is associated with an unacceptably high frequency of allergic reactions. However, recent studies suggest that OIT might be made safer and faster when performed in conjunction with anti-IgE monoclonal antibody as an adjunctive treatment.Expert Review of Clinical Immunology 08/2014; 10(9). DOI:10.1586/1744666X.2014.948849 · 3.34 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Rhinosinusitis affects an estimated one in seven adults in the United States. Otolaryngologists are intimately involved in the care of patients with rhinosinusitis and other upper airway inflammatory conditions through procedures such as endoscopic sinus surgery and, therefore, would benefit from a deeper understanding of the associated comorbidities and their management. Recent evidence has suggested several connections between the underlying disease of rhinosinusitis, seasonal allergies, and food allergies. The authors of the present review seek to provide a focused analysis of the recent literature with respect to epidemiology, pathophysiology, and treatment options concerning these conditions. Evidence has connected the function of filaggrin, a skin barrier protein, with the pathogenesis of allergic rhinosinusitis and food allergy. Additionally, decreased levels of regulatory B cells and T cells are associated with and play a role in atopic disease. Overlapping treatment modalities between these conditions suggest similar conclusions. Future research into the role of the skin barrier, regulatory immune cell functioning, transforming growth factor-β, and other cytokine signaling, and treatment options such as omalizumab and azelastine is likely to have profound impact on clinicians' management of patients with these disorders and their comorbidities.Current Opinion in Otolaryngology & Head and Neck Surgery 02/2015; 23(1):2-7. DOI:10.1097/MOO.0000000000000123 · 1.39 Impact Factor
Journal of Allergy and Clinical Immunology 09/2014; 134(3). DOI:10.1016/j.jaci.2014.05.043 · 11.25 Impact Factor