Background: Peanut allergy is the leading cause of food-related anaphylaxis, and accidental exposures are common. Oral immunotherapy (OIT) has been posited as a potential treatment. Methods: Patients aged 3–65 years with peanut-specific IgE ≥7 kU/l and/or a positive skin prick test with a history of an allergic reaction to peanut were recruited to undergo an OIT protocol. All adverse reactions were recorded by research staff or patients in real time. Results: Twenty-four patients received 6,662 doses. Symptoms were mostly mild (84%), and only 3 severe gastrointestinal reactions required the administration of epinephrine. Abdominal pain was the most common reaction, followed by oropharyngeal and lip pruritus. Respiratory symptoms were rare. Conclusions: In this trial of OIT in adults and children, most reactions were mild.
Background-Peanut allergy is the leading cause of food-related anaphylaxis and accidental exposures are common. Oral immunotherapy has been posited as a potential treatment.
RationaleOur main focus in the laboratory is to understanding the mechanisms of how oral immunotherapy (OIT) improves outcomes in patients. In this study, we aimed to determine if OIT is specific only to the food allergens administered in OIT or also to other offending allergens (i.e. "bystander effect"). To accomplish our aim, we studied T cell reactivity (i.e. proliferation assays) and T cell specificity (i.e. tetramer assays with peanut peptides) in both effector T cell (CD4+CD25neg) or Teff and regulatory T cell (CD4+CD25hiFoxp3+) or Treg subsets.
MethodsA phase I trial of oral immunotherapy for peanut allergy was approved by the Stanford IRB and conducted according to ICH guidelines. All subjects (n=24) had a moderate to severe clinical reactions to peanut ingestion, peanut-specific IgE ≥ 15 kU/L, and a positive skinprick test. Subjects underwent an initial dose escalation to a maximum dose prior to initiating daily home dosing with q2wk dose. Blood samples were collected at baseline and throughout the course of the treatment. T cells were magnetically purified and tested for specificity to peanut epitopes, other offending food allergens for the patient, and a control antigen. Basophil reactivity was also assessed using a whole blood assay. Clinical assessments were performed using Bock's criteria.
ResultsTwenty-four subjects, ages 5 to 45, have received 3777 doses. Teff cell proliferation (using 3H thymidine assays) was optimally suppressed by autologous Treg when activation occurred using antigen presenting cells (APCs) loaded with peanut, rather than loaded with other offending food allergens (i.e. milk). Basophil reactivity (as determined by CD203c) was downregulated during the course of OIT to both peanut and other offending allergens.
ConclusionsWe report on our immune monitoring results to date at Stanford Hospital and Clinics with a phase I peanut oral immunotherapy study using published methods. With T cell monitoring, we were able to show downregulation of specific peanut-induced proliferation and that this downregulation was mediated by Treg specific to peanut epitopes.
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