JAK1 inhibition with abrocitinib decreases allergen-specific basophil and T-cell activation in pediatric peanut allergy

Nicole Ramsey, Wajiha Kazmi, Matthew Phelan, Daniel Lozano-Ojalvo, M. Cecilia Berin

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: JAK1 is a signaling molecule downstream of cytokine receptors, including IL-4 receptor α. Abrocitinib is an oral JAK1 inhibitor; it is a safe and effective US Food and Drug Administration–approved treatment for adults with moderate-to-severe atopic dermatitis. Objective: Our objective was to investigate the effect of abrocitinib on basophil activation and T-cell activation in patients with peanut allergy to determine the potential for use of JAK1 inhibitors as a monotherapy or an adjuvant to peanut oral immunotherapy. Methods: Basophil activation in whole blood was measured by detection of CD63 expression using flow cytometry. Activation of CD4+ effector and regulatory T cells was determined by the upregulation of CD154 and CD137, respectively, on anti-CD3/CD28– or peanut-stimulated PBMCs. For the quantification of peanut-induced cytokines, PBMCs were stimulated with peanut for 5 days before harvesting supernatant. Results: Abrocitinib decreased the allergen-specific activation of basophils in response to peanut. We showed suppression of effector T-cell activation when stimulated by CD3/CD28 beads in the presence of 10 ng of abrocitinib, whereas activation of regulatory T-cell populations was preserved in the presence of abrocitinib. Abrocitinib induced statistically significant dose-dependent inhibition in IL-5, IL-13, IL-10, IL-9, and TNF-α in the presence of peanut stimulation. Conclusion: These results support our hypothesis that JAK1 inhibition decreases basophil activation and TH2 cytokine signaling, reducing in vitro allergic responses in subjects with peanut allergy. Abrocitinib may be an effective adjunctive immune modulator in conjunction with peanut oral immunotherapy or as a monotherapy for individuals with food allergy.

Original languageEnglish
Article number100103
JournalJournal of Allergy and Clinical Immunology: Global
Volume2
Issue number3
DOIs
StatePublished - Aug 2023

Keywords

  • Abrocitinib
  • JAK1
  • allergen-specific T cell
  • basophil activation
  • peanut allergy

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