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Bruton's Tyrosine Kinase (Btk) Inhibitor Tirabrutinib Prevents the Development of Murine Lupus

Systemic Lupus Erythematosus (SLE) is a complex and heterogeneous autoimmune disease associated with the over production of high affinity autoantibodies. Over- activity of B-cell responsiveness to immune stimulation and direct activation of circulating FcR bearing cells are sufficient to initiate inflammatory responses, which may be an essential feature of SLE pathogenesis. Here, we examined the potential efficacy of tirabrutinib using NZB/WF1 and MRL/lpr mice within the model of spontaneous SLE. Tirabrutinib inhibited the assembly of anti-dsDNA in serum, and therefore the onset of proteinuria resulted in markedly lower in both lupus-prone mice. Furthermore, the treatment with tirabrutinib resulted in 100% survival, while 70% survival was observed in untreated mice. Significant reductions in the numbers of total IgG and anti-dsDNA- secreting B-cells were apparent in spleens from tirabrutinib treated mice.