Syk inhibition with fostamatinib leads to transitional B lymphocyte depletion

Academic Article

Abstract

  • 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. © 2012 Elsevier Inc.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Barr PM; Wei C; Roger J; Schaefer-Cutillo J; Kelly JL; Rosenberg AF; Jung J; Sanz I; Friedberg JW
  • Start Page

  • 237
  • End Page

  • 242
  • Volume

  • 142
  • Issue

  • 3