Kinetics of basophil hyporesponsiveness during short-course peanut OIT

• Type of Material: Article
• Authors: Michael D. Kulis, University of North Carolina, Chapel Hill; Johanna M. Smeekens, University of North Carolina, Chapel Hill; Caitlin Burk, Massachusetts General Hospital; Xiaohong Yue, University of North Carolina, Chapel Hill; Rishu Guo, University of North Carolina, Chapel Hill; Kelly A. Orgel, University of North Carolina, Chapel Hill; Ping Ye, University of North Carolina, Chapel Hill; Lauren Herlihy, University of North Carolina, Chapel Hill; Deanna Hamilton, University of North Carolina, Chapel Hill; Quefeng Li, University of North Carolina, Chapel Hill; Corinne Keet, University of North Carolina, Chapel Hill; Wayne Shreffler, Massachusetts General Hospital; Brian P. Vickery, Emory University; A. Wesley Burks, University of North Carolina, Chapel Hill; Edwin H. Kim, University of North Carolina, Chapel Hill
• Language: English
• Date: 2022-06-16
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 American Academy of Allergy, Asthma & Immunology
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): https://doi.org/10.1016/j.jaci.2022.05.020
• Title of Journal or Parent Work: Journal of Allergy and Clinical Immunology
• Volume: 150
• Issue: 5
• Start Page: 1144
• End Page: 1153
• Grant/Funding Information: This work was supported by the National Institutes of Health (NIAID) R01-AI068074. JMS was funded by a T32 Allergy/Immunology Training Grant (AI007062) through Duke University and University of North Carolina at Chapel Hill. The UNC Flow Cytometry Core Facility is supported in part by P30 CA016086 Cancer Center Core Support Grant to the UNC Lineberger Comprehensive Cancer Center.
• Keywords: Oral immunotherapy; Basophil activation; Food allergy; Peanut allergy; pSYK
• Research Categories: Health Sciences, Immunology

Abstract

Background: Oral immunotherapy (OIT) leads to suppression of mast cell and basophil degranulation along with changes in the adaptive immune response. Objective: We aimed to determine how rapidly these effects occur during OIT and more broadly, the kinetics of basophil and mast cell suppression throughout the course of therapy. Methods: Twenty participants, aged 4–12, were enrolled in a peanut OIT trial and assessed for desensitization and sustained unresponsiveness (SU) after nine months of therapy. Blood was collected five times in the first month and then intermittently throughout to quantify immunoglobulins and assess basophil activation by CD63, CD203c, and phosphorylated SYK (pSYK). Results: Twelve of sixteen participants that completed the trial were desensitized after OIT, with nine achieving SU after discontinuing OIT for four weeks. Basophil hyporesponsiveness, defined by lower CD63 expression, was detected as early as day 90. pSYK was correlated with CD63 expression and there was a significant decrease in pSYK by day 250. CD203c expression remained unchanged throughout therapy. Interestingly, although basophil activation was decreased across the cohort during OIT, basophil activation did not correlate with individual clinical outcomes. Serum peanut-specific IgG4 and IgA increased throughout therapy, whereas IgE remained unchanged. Conclusion: Suppression of basophil activation occurs within the first 90 days of peanut OIT, ultimately leading to suppression of signaling through pSYK.