INTRODUCTION: Systemic lupus erythematosus is a chronic autoimmune disease 
characterized by an abundance of autoantibodies against nuclear antigens. 
Bruton's tyrosine kinase (Btk) is a proximal transducer of the BCR signal that 
allows for B-cell activation and differentiation. Recently, selective inhibition 
of Btk by PCI-32765 has shown promise in limiting activity of multiple cells 
types in various models of cancer and autoimmunity. The aim of this study was to 
determine the effect of Btk inhibition by PCI-32765 on the development of lupus 
in lupus-prone B6.Sle1 and B6.Sle1.Sle3 mice.
METHODS: B6.Sle1 or B6.Sle1.Sle3 mice received drinking water containing either 
the Btk inhibitor PCI-32765 or vehicle for 56 days. Following treatment, mice 
were examined for clinical and pathological characteristics of lupus. The effect 
of PCI-32765 on specific cell types was also investigated.
RESULTS: In this study, we report that Btk inhibition dampens humoral 
autoimmunity in B6.Sle1 monocongenic mice. Moreover, in B6.Sle1.Sle3 bicongenic 
mice that are prone to severe lupus, Btk inhibition also dampens humoral and 
cellular autoimmunity, as well as lupus nephritis.
CONCLUSIONS: These findings suggest that partial crippling of cell signaling in 
B cells and antigen presenting cells (APCs) may be a viable alternative to total 
depletion of these cells as a therapeutic modality for lupus.