TY - JOUR
T1 - CD20, AIF-1, and TGF-Β in graft-versus-host disease
T2 - A study of mRNA expression in histologically matched skin biopsies
AU - Wu, Julie M.
AU - Thoburn, Christopher J.
AU - Wisell, Joshua
AU - Farmer, Evan R.
AU - Hess, Allan D.
N1 - Funding Information:
This study was supported by Grant CA15396, from National Cancer Institute (National Institutes of Health).
PY - 2010/5
Y1 - 2010/5
N2 - 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.
AB - 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.
KW - AIF-1
KW - CD20
KW - Cytokines
KW - Graft-versus-host disease
KW - Skinbiopsy
UR - http://www.scopus.com/inward/record.url?scp=77952008607&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952008607&partnerID=8YFLogxK
U2 - 10.1038/modpathol.2010.48
DO - 10.1038/modpathol.2010.48
M3 - Article
C2 - 20190732
AN - SCOPUS:77952008607
SN - 0893-3952
VL - 23
SP - 720
EP - 728
JO - Modern Pathology
JF - Modern Pathology
IS - 5
ER -