Immunologic Trajectories of Peanut Desensitization (INROADS) - SUMMARY – Overall Application: Immunologic Trajectories of Peanut Desensitization (INROADS) Peanut allergy has tripled in prevalence in recent decades, affecting nearly 2% of adults and up to 5% of children in some US regions. Peanut allergy is typically lifelong, can be fatal, and impacts quality of life. Our group and others performed the studies resulting in the recent FDA approvals of a commercial peanut oral immunotherapy (OIT) and an anti-IgE monoclonal antibody, omalizumab. These therapies can raise the reaction threshold and provide safety from accidental exposures for approximately 67% of patients. Additionally, in a prior period of our AADCRC grant, we focused on children whose reaction threshold to peanut was higher than the children included in the registration trials of the expensive pharmaceutical products. We demonstrated that nearly half of the peanut allergic population could be treated safely and effectively with inexpensive, retail store-purchased, home-measured peanut. These findings are revolutionizing desensitization therapy for peanut allergy and provide options for our patients other than strict peanut avoidance. However, in clinical practice, there is no way to predict response to therapy, and there is an insufficient understanding of the mechanisms that are involved in the success, or lack thereof, from these therapies. This proposal, Immunologic Trajectories of Peanut Desensitization (INROADS), builds upon discoveries and techniques from our prior AADCRC and our additional studies to address the knowledge gaps of these desensitization therapies that will improve personalized care and provide mechanistic insights for better treatments. INROADS will address the overarching hypothesis that dynamic changes in circulating cellular subpopulations and molecular networks are mechanistically linked to peanut desensitization outcomes. Project 1, MICRO-TRACK, will use high-dimensional immune profiling, allergen- specific T cell assays, and in vitro stimulation models to identify predictive biomarkers and mechanisms of immunologic control of desensitization therapies. Project 2, SPADE, will complement this effort using transcriptomics and machine learning to identify signatures of desensitization and desensitization classifiers to provide mechanistic insights and clinical tools for treating individuals with peanut allergy. We will synergize Mount Sinai’s cutting-edge clinical therapeutics program via a Clinical Core (PATHWAYS) to provide clinical data and biosamples from oral food challenge tests performed before and following desensitization treatments. The two research projects, interactions with the Clinical Core, management of biosamples and data, and communications with NIAID and the AADCRC network will be coordinated and supported by an Administrative Core and a Data Stewardship Core. In addition to creating a rich resource of clinical, immune, and molecular data that will be made publicly available for the research community, our integrated program will advance personalized medicine, enrich mechanistic understandings, and potentially identify new therapeutic targets for peanut allergy that will be informative for allergy to any food.
