Oral immunotherapy with omalizumab reverses the Th2 cell-like programme of regulatory T cells and restores their function.

BACKGROUND: Oral immunotherapy (OIT) successfully desensitizes patients with food allergies, but the immune mechanisms mediating its efficacy remain obscure. OBJECTIVES: We tested the hypothesis that allergen-specific regulatory T (Treg) cell function is impaired in food allergy and is restored by anti-IgE antibody (omalizumab)-supplemented OIT. METHODS: Peanut-specific T effector (Teff) and Treg cell proliferative responses, activation markers and cytokine expression were analysed by flow cytometry in 13 peanut-allergic subjects before the start of omalizumab-supplemented OIT and periodically in some subjects thereafter for up to 2 years. Peripheral blood regulatory T cells (Treg cells) were analysed for their peanut-specific suppressor function before and at 1 year following OIT. This study was registered on ClinicalTrials.gov (NCT01290913). RESULTS: Proliferation of allergen-specific Teff and Treg cells precipitously declined following the initiation of omalizumab therapy prior to OIT, followed by partial recovery after the initiation of OIT. At baseline, peanut-specific Treg cells exhibited a Th2 cell-like phenotype, characterized by increased IL-4 expression, which progressively reversed upon OIT. Peanut-specific Treg cell suppressor activity was absent at the start of omalizumab/OIT therapy but became robust following OIT. Absent peanut-specific Treg cell function could also be recovered by the acute blockade of IL-4/IL-4R receptor signalling in Treg cells, which inhibited their IL-4 production. CONCLUSIONS AND CLINICAL RELEVANCE: OIT supplemented by omalizumab promotes allergen desensitization through an initial omalizumab-dependent step that acutely depletes allergen-reactive T cells, followed by an increase in allergen-specific Treg cell activity due to the reversal of their Th2 cell-like programme. Improved Treg cell function may be a key mechanism by which OIT ameliorates food allergy.

An audit of low dose triple therapy for eradication of Helicobacter pylori.

AIMS: Standard triple therapy remains the recommended first line treatment for Helicobacter pylori in New Zealand. The real eradication rate achieved in busy hospital clinics may be different from data obtained from clinical trials outside of New Zealand. METHODS: One hundred and thirty patients with proven H pylori infection (by at least two tests) were treated with low dose triple therapy (DeNol 1 qid, tetracycline 250 mg qid and metronidazole 200 mg qid for 2 weeks; dosing with meals and at night); 83 were given a standard prescription for triple therapy (dispensed in bottles) and 47 were given a medication pack with times of dosing clearly marked. Eradication was proven by a negative 13C urea breath test at least 4 weeks after finishing treatment. RESULTS: Follow up urea breath test was obtained in 120 patients (92%). The eradication rate for separate bottles was 79% and for the medication pack 76%. Compliance was estimated to be greater than 90% in 92% of patients who attended for followup. H pylori culture and sensitivity results were available for 41 patients. Overall rate of metronidazole resistance was 32%. The eradication rate for metronidazole sensitive strains was 89% and for resistant strains 46%. Mild side effects were reported in 10% and moderate side effects in 10%. No patient stopped treatment because of side effects. There was no effect of age, ethnicity, smoking, alcohol intake, pretreatment with H2-antagonists or endoscopic diagnoses on eradication rates. CONCLUSION: The low dose triple therapy has an acceptable real eradication rate. The most important determinant of success was metronidazole resistance. The eradication rate was not improved by using medication packs.