BUSCADOR RECOLECTA

[Background] JAK1 is a signaling molecule downstream of cytokine receptors including IL- 4R alpha. Abrocitinib is an oral JAK1 inhibitor and is a safe and effective FDA 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 peanut allergic patients to determine the potential for use of JAK1 inhibitors as a monotherapy or as 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 (Tregs) 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 prior to harvesting supernatant., [Results] Abrocitinib decreased the allergen-specific activation of basophils in response to peanut. Results show suppression of effector T cell activation when stimulated by CD3/CD28 beads in the presence of 10 ng of Abrocitinib, while activation of Treg populations was preserved in the presence of Abrocitinib. Abrocitinib induced a statistically significant dose dependent inhibition in IL-5, IL-13, IL-10, IL-9, and TNF alpha 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 food allergic individuals., Peer reviewed