Immune progression and plasticity in relation to child age

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Oral immunotherapy (OIT) for peanut allergy has been the most studied interventional strategy for children with established allergy and is now the focus of an industry-sponsored phase 3 trial – one of the first in a field currently lacking any approved therapy. For the majority of patients treated, they can tolerate OIT adequately and it induces a substantial shift in the dose of allergen that elicits a reaction to a level well above most accidental ingestions, so long as they maintain consistent therapeutic exposure. This transient state of clinical protection, or `desensitization' as it is often referred to by allergists, is deemed an acceptable outcome by many patients, but there are limitations. For one, when in a desensitized state, unlike someone who is in true remission, there is some ongoing risk of treatment-associated reactions, especially with co-factors of inter-current illness, exercise, NSAID use, and others. Secondly, many patients find it very difficult to adhere to a chronic therapy. Therefore, even without the goal of ad lib peanut consumption, OIT would be a more beneficial intervention if efficacy were more durable and easier to maintain after an initial course of treatment. In fact, from several studies of children from school age and above, about 1/3 of patients do achieve a more durable benefit from OIT, defined by being able to avoid peanut for a month or more and remaining clinical tolerant to a clinically significant exposure. Those patients who achieve this more robust benefit tend to have lower peanut specific IgE levels at baseline, suggesting that there may be important immunological differences about them, but they are otherwise hard to identify. A just published study, however, suggests that young age at the time of OIT may also be associated with persistent tolerance after immunotherapy. This proposal would directly test the hypothesis that younger patients achieve OIT-induced tolerance at higher rates and would generate the clinical data and samples necessary to explore the immune mechanisms of age-dependent disparities.