CD20, AIF-1, and TGF-Β in graft-versus-host disease: A study of mRNA expression in histologically matched skin biopsies

Julie M. Wu, Christopher J. Thoburn, Joshua Wisell, Evan R. Farmer, Allan D. Hess

Research output: Contribution to journalArticle

Abstract

Graft-versus-host disease is the leading cause of non-relapse mortality after allogeneic bone marrow transplantation. The cell-mediated immune mechanisms that underlie the pathogenesis of graft-versus-host disease remain unclear. In this study, 47 skin biopsies representing graft-versus-host disease grades 0-III, lichenoid, and sclerodermoid were included from 31 allogeneic bone marrow transplantation recipients. RNA from paraffin-embedded tissue was harvested. Transcript levels of the following markers were assessed and correlated with grade and survival: CD3, CD20, FoxP3, IL-17, γ-interferon (IFN-γ), transforming growth factor-β (TGF-β), IL-6, connective tissue growth factor (CTGF), allograft inflammatory factor-1(AIF-1), and IL-13. Levels of three markers significantly correlated with the length of survival (TGF-β, correlation coefficient 20.8, P0.016; AIF-1, 13.2, P0.016; and CD20, 66, P0.027). CD20 expression was limited to lichenoid cases. Levels of TGF-β, AIF-1, and IFN-γ appeared to correlate with histological progression, but did not reach statistical significance. Expression of FoxP3 correlated with worse survival, and approached statistical significance (P0.053). Two potential mechanistic pathways were identified: the scleroderma group (AIF-1 and TGF-β) and the B-cell group (CD20). Transcript levels of these markers were implicated in the progression from acute to chronic disease, and also correlated significantly with the duration of survival. Identification of these three markers may direct therapy selection with targeted agents, including the use of rituximab when B-lymphocytes are implicated.

Original languageEnglish (US)
Pages (from-to)720-728
Number of pages9
JournalModern Pathology
Volume23
Issue number5
DOIs
StatePublished - May 1 2010

Keywords

  • AIF-1
  • CD20
  • Cytokines
  • Graft-versus-host disease
  • Skinbiopsy

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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