Remibrutinib inhibits hives effector cells stimulated by serum from chronic urticaria patients independently of FcεR1 expression level and omalizumab clinical response

Autor: Ramón Gimeno, Clara Ribas‐Llauradó, David Pesque, Evelyn Andrades, Bruno Cenni, Barbara Ambros, Ramon Pujol, Ana M. Giménez‐Arnau
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Clinical and Translational Allergy, Vol 13, Iss 3, Pp n/a-n/a (2023)
Druh dokumentu: article
ISSN: 2045-7022
DOI: 10.1002/clt2.12227
Popis: 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, FcεR1a 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.
Databáze: Directory of Open Access Journals
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