Monitoring clinical response to immunomodulatory treatments Jyothi Tirumalasetty, Rose Madison, Reena Rajcoomar, Laurie Kost, Katharine Fast, Jessica Rogers, Ilan Bocian, Andrew R. Chin, Andrew Long, R. Sharon Chinthrajah, and Sayantani B. Sindher, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, United States © 2022 Elsevier Inc. All rights reserved. Introduction 1 Testing methods for the diagnosis and monitoring of food allergy 2 Mast cell activation testing (MAT) 4 Quality of life 4 Safety 5 Oral immunotherapy 5 Epicutaneous immunotherapy and sublingual immunotherapy 6 Biologics 7 Conclusion 8 Acknowledgments 8 Conflict of Interest 9 References 9 Key points • Oral immunotherapy, epicutaneous immunotherapy, sublingual immunotherapy, and monoclonal antibody therapies for the treatment of food allergies induce desensitization at various levels. • Testing methods used for diagnosis and monitoring include DBPCFC, specific IgE, skin prick test, specific IgG4, basophil activation test, mast cell activation test, CD4 þ T cell responses, quality of life scores, and safety data. • Various testing methods can provide useful information on mechanisms and management however the DBPCFC continues to be the gold standard test for monitoring the response to food immunotherapy. Abstract Food allergy is increasing in prevalence and continues to have detrimental impacts on quality of life. Multiple modalities of food immunotherapy have emerged over recent years, however, the mechanisms behind these treatments are not fully understood. Testing prior, during, and after food immunotherapy has helped to elucidate mechanisms, monitor response, and predict outcomes. Despite the availability of various testing methods, the DBPCFC continues to be the gold standard for reliably monitoring response to food immunotherapy. Introduction Approximately 33 million adults and children in the United States have persistent, life-threatening food allergies (Gupta et al., 2018, 2019). In the United States, United Kingdom, and Australia, the prevalence of food allergy is increasing but treatment options have been limited until recent years (Sampath et al., 2021). Traditional management of food allergies has been limited to strict food allergen avoidance and emergency treatment plans with self-injectable epinephrine, however, frequent accidental ingestions and subsequent reactions can lead to decreased quality of life (Patel et al., 2017). In recent years, several methods of immunotherapy have emerged as important treatment options for patients with food allergies (Fig. 1). The goal of food immunotherapy is to desen- sitize the immune system to a food allergen and increase the threshold dose that could trigger a reaction. Given the safety and effec- tiveness shown in multiple OIT studies, the FDA approved the use of peanut (Arachis hypogaea) allergen powder-dnfp for oral immunotherapy (OIT) in peanut allergic patients in 2020. In the majority of peanut allergic patients, peanut OIT increases the amount of peanut protein a patient can be exposed to before an allergic reaction may occur (PALISADE Group of Clinical Inves- tigators et al., 2018). Food OIT can improve quality of life and food allergy related anxiety, however it has also been associated with frequent adverse reactions, primarily gastrointestinal symptoms, and less frequently, systemic reactions (Vickery et al., 2021). In addition to OIT, two additional allergen specific food immunotherapy options, epicutaneous immunotherapy (EPIT), sublingual immunotherapy (SLIT), have emerged as promising treatments options for food allergy in recent years. EPIT is unique Reference Collection in Food Science https://doi.org/10.1016/B978-0-323-96018-2.00026-2 1