Syk inhibition with fostamatinib leads to transitional B lymphocyte depletion

Cell signaling initiated by the B cell receptor is critical to normal development of B lymphocytes, most notably at the transitional B cell stage. Inhibition of this signaling pathway with the syk inhibitor, fostamatinib, has produced significant efficacy in lymphoid malignancies and autoimmune conditions. Here, we demonstrate that short-term use of fostamatinib impairs B lymphocyte development at the transitional stage without affecting mature B cell populations. Additionally, IL-10 producing B cells remained relatively constant throughout the treatment period. These findings provide insight into the mechanism of action of B cell receptor inhibition in autoimmune disease. As the development of agents targeting B cell receptor signaling proceeds, monitoring for long-term consequences as well as functional evaluation of B cell subsets may further improve our understanding of this rapidly growing class of novel agents.

► Agents targeting B cell receptor signaling have demonstrated significant efficacy.
► We examined the effects of fostamatinib on normal B lymphocytes.
► Short term syk inhibition does not affect mature B cell populations.
► Peripheral blood transitional B cell populations are depleted with fostamatinib.
► IL-10 producing B cells are unaffected with fostamatinib.