Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcepsilonR1 expression level and omalizumab clinical response.
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Gimeno R, Ribas-Llaurado C, Pesque D, Andrades E, Cenni B, Ambros B, Pujol R, Gimenez-Arnau AM
Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcepsilonR1 expression level and omalizumab clinical response.
Clin Transl Allergy. 2023 Mar;13(3):e12227. doi: 10.1002/clt2.12227.
- PubMed ID
- 36973953 [ View in PubMed]
- Abstract
BACKGROUND: Despite advances in the treatment of chronic urticaria, in a significant percentage of the patients symptoms are not fully controlled with conventional approaches. New strategies under development include blocking intracellular mediators of mast cell and basophil activation. OBJECTIVE: We aim to investigate the effects of the Bruton's tyrosine kinase (BTK) inhibitor remibrutinib on human blood basophils and CD34(+) -derived mast cells activation induced by serum obtained from chronic urticaria patients. METHODS: Twenty-two patients with chronic spontaneous urticaria (mean age 52 years, 27% women) and 22 patients with chronic inducible urticaria (46 years, 27% women) were included in the study together with a sex-matched control group. Patients were classified as responders or non-responders to anti-IgE therapy on the basis of their clinical data, FcepsilonR1a expression on blood basophils and total IgE levels. Changes on CD63 expression-as an activation marker-, were used to evaluate in vitro the response of basophils and mast cells to serum exposure and the inhibitory effects of remibrutinib. RESULTS: Remibrutinib inhibits degranulation induced by IgE cross-linking in mast cells and basophils and also the activation triggered by factors present in the sera of spontaneous and inducible chronic urticaria patients. Patient's serum induces a greater degranulation of effector cells than controls. Activation of mast cells and basophils by patient sera and remibrutinib effects were not related to omalizumab responsiveness. CONCLUSION: Remibrutinib inhibits activation of human basophils and mast cells induced in vitro by exposure to the serum of chronic urticaria patients independently of their response to omalizumab.