Effect of anti-IgE therapy on food allergen specific T cell responses in eosinophil associated gastrointestinal disorders.

BACKGROUND: Anti-IgE therapy inhibits mast cell and basophil activation, blocks IgE binding to both FcεRI and CD23 and down regulates FcεRI expression by antigen (Ag) presenting cells (APCs). In addition to its classical role in immediate hypersensitivity, IgE has been shown in vitro to facilitate Ag presentation of allergens, whereby APC bound IgE preferentially takes up allergens for subsequent processing and presentation. The purpose of this study was to determine whether anti-IgE therapy, by blocking facilitated Ag presentation in vivo, attenuates allergen specific Th2 cell responses. METHODS: To test this hypothesis, food allergen specific T cell responses were examined during a 16-week clinical trial of omalizumab in nine subjects with eosinophilic gastroenteritis and food sensitization. Allergen specific T cell responses were measured using carboxyfluorescein succinimidyl ester dye dilution coupled with intracellular cytokine staining and polychromatic flow cytometry. Four independent indices of allergen specific T cell response (proliferation, Ag dose response, precursor frequency, and the ratio of Th2:Th1 cytokine expression) were determined. RESULTS: Eight of the 9 subjects had measurable food allergen specific responses, with a median proliferation index of 112-fold. Allergen specific T cell proliferation was limited to CD4 T cells, whereas CD8 T cell did not proliferate. Food allergen specific responses were Th2 skewed relative to tetanus specific responses in the same subjects. In contradistinction to the original hypothesis, anti-IgE treatment did not diminish any of the four measured indices of allergen specific T cell response. CONCLUSIONS: In sum, using multiple indices of T cell function, this study failed to demonstrate that anti-IgE therapy broadly or potently inhibits allergen specific T cell responses. As such, these data do not support a major role for IgE facilitated Ag presentation augmenting allergen specific T cell responses in vivo. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT00084097.

Anti-IgE treatment of eosinophil-associated gastrointestinal disorders.

BACKGROUND: Eosinophil-associated gastrointestinal disorders (EGIDs) are commonly associated with atopy and are being recognized with increasing frequency. Current therapy for EGIDs is inadequate. OBJECTIVE: We sought to determine the efficacy of anti-IgE therapy in EGIDs and investigate the role of IgE in disease pathogenesis. METHODS: Nine subjects with EGIDs received omalizumab every 2 weeks for 16 weeks while other therapy was held constant. Blood absolute eosinophil counts, tissue eosinophil counts, symptom scores, and free IgE levels were serially measured. Allergen skin testing and flow cytometry for basophil activation and FcepsilonRI were determined at baseline and at week 16. RESULTS: Omalizumab was associated with a decrease in absolute eosinophil count at both the week 16 (34%, P = .004) and combined weeks 12 to 16 (42%, P = .012) time points. Tissue eosinophils decreased in the duodenum (59%) and gastric antrum (69%) but did not reach statistical significance (P = .074 and .098, respectively). Esophageal eosinophil counts remained unchanged. Basophil and dendritic cell FcepsilonRI expression and free IgE levels were all significantly decreased (P < .005). Omalizumab increased the concentration of allergen required to trigger half-maximal basophil activation by 170-fold. Allergen skin test wheal and erythema responses decreased by 78% and 82%, respectively. Symptom scores were decreased at both the midstudy (63%) and end of study (70%) time points (P < .005 for both). CONCLUSION: These results demonstrate that IgE-mediated processes contribute to the generation of eosinophilic inflammation in EGIDs and suggest that anti-IgE therapy might be effective in these disorders. CLINICAL IMPLICATIONS: Anti-IgE might be a potential therapy for EGIDs.

Advances in pediatric asthma and atopic dermatitis.

PURPOSE OF REVIEW: Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. RECENT FINDINGS: With increasing options for the treatment of allergic diseases, much work is now focused on methods for individualizing treatments to a patient's phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regimens for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extends to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. SUMMARY: Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patient-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review.