Effects of ibrutinib on effector B cells in patients with systemic sclerosis

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URI: http://hdl.handle.net/10900/123462
Dokumentart: PhDThesis
Date: 2022-01-21
Source: Einhaus, J., Pecher, A., Asteriti, E., Schmid, H., Secker, KA., Duerr-Stoerzer, S., Keppeler, H., Klein, R., Schneidawind, C., Schneidawind, D., 2020. Inhibition of effector B cells by ibrutinib in systemic sclerosis. Arthritis Res Ther 22:66. https://doi.org/10.1186/s13075-020-02153-8
Language: English
Faculty: 4 Medizinische Fakultät
Department: Medizin
Advisor: Schneidawind, Dominik (PD Dr.)
Day of Oral Examination: 2021-03-12
DDC Classifikation: 610 - Medicine and health
Other Keywords: Systemsklerose
B cells
Systemic sclerosis
License: http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en
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Systemic sclerosis (SSc) is a connective tissue disease with significant morbidity and reduced survival of patients. Currently available treatment strategies only alleviate symptoms and slow disease progression. Previous attempts of immunomodulating therapies addressing B cell pathology like rituximab and tocilizumab in SSc showed insufficient efficacy. Here, we investigated the therapeutic potential of ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor used in B cell malignancies, to alter B cell pathology in SSc in an in vitro model of autoimmunity. Our data show that ibrutinib was able to reduce the production of the profibrotic hallmark cytokines IL-6 and TNF-α, which are mainly released by the effector B cell population, in response to TLR9-stimulation, while preserving the release of immunoregulatory IL-10 and IFN-γ from B cells. This investigation supports efforts for a potential future clinical application of ibrutinib in patients with SSc as a novel treatment for the underlying pathogenetic immune imbalance contributing to disease onset and progression.

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