Altered Toll-Like Receptor 9 Responses in Circulating B Cells at the Onset of Extensive Chronic Graft-versus-Host Disease

Academic Article

Abstract

  • B cells appear to play a role in chronic graft-versus-host disease (cGVHD) as shown in murine models and the success of anti-CD20 B cell antibody treatment in humans. Recent studies have shown that immunostimulatory microbial CpG-DNA splenic responses were enhanced in murine GVHD. We hypothesized that CpG-induced B cell responses are increased in human cGVHD. Newly diagnosed cGVHD patients enrolled on the COG protocol ASCT0031 were divided into early (3-8 months postblood and marrow transplant [BMT]) and late (≥9 months post-BMT) onset groups and compared to time-matched control BMT patients. A significantly greater percentage of phosphorothioate (PS)-modified CpG stimulated B cells from cGVHD patients demonstrated an increased expression of CD86 compared to controls (P = .0004). This response had a significant correlation between B cell TLR9 expression (r 2 = 0.65; P = .002) and CD86 upregulation using the entirely TLR9-dependent native phosphodiester CpG (P = .003). The PS-modified CpG response at 2 months after initiation of cGVHD therapy demonstrated a trend toward predicting therapeutic response at 9 months post-BMT (P = .07). These findings suggest that an increased number of B cells, primed for a TLR9 response, may play a role in the pathophysiology of cGVHD. © 2007 American Society for Blood and Marrow Transplantation.
  • Digital Object Identifier (doi)

    Author List

  • She K; Gilman AL; Aslanian S; Shimizu H; Krailo M; Chen Z; Reid GS; Wall D; Goldman F; Schultz KR
  • Start Page

  • 386
  • End Page

  • 397
  • Volume

  • 13
  • Issue

  • 4