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

Abstract

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.