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

Autor: Gimeno R; Laboratory of Immunology, Department of Pathology, Hospital del Mar, Barcelona, Spain.; Department Immnology, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain., Ribas-Llauradó C; Department Immnology, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain., Pesque D; Department of Dermatology, Hospital del Mar, IMIM, Universitat Pompeu Fabra, Barcelona, Spain., Andrades E; Department Immnology, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Department of Dermatology, Hospital del Mar, IMIM, Universitat Pompeu Fabra, Barcelona, Spain., Cenni B; Department of Research, BC Novartis Institutes for BioMedical Research, Novartis, Basel, Switzerland., Ambros B; Department of Clinical Development, BA Global Drug Development, Novartis, Basel, Switzerland., Pujol R; Department Immnology, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.; Department of Dermatology, Hospital del Mar, IMIM, Universitat Pompeu Fabra, Barcelona, Spain., Giménez-Arnau AM; Department Immnology, Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.; Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Barcelona, Spain.; Department of Dermatology, Hospital del Mar, IMIM, Universitat Pompeu Fabra, Barcelona, Spain.
Jazyk: angličtina
Zdroj: Clinical and translational allergy [Clin Transl Allergy] 2023 Mar; Vol. 13 (3), pp. e12227.
DOI: 10.1002/clt2.12227
Abstrakt: 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.
(© 2023 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)
Databáze: MEDLINE
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