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The Involvement of Epithelial Fas in a Human Model of Graft Versus Host Disease

Lookup NU author(s): Dr Shaheda Ahmed, Dr Xiao WangORCiD, Professor Graham Jackson, Professor Anne Dickinson

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Abstract

Background. Graft-versus-host disease (GVHD) is an important complication occurring after hematopoietic stem-cell transplantation (HSCT). Animal model studies have shown the involvement of the Fas (APO-1/CD95)/Fas-Ligand pathway in GVHD pathogenesis, but its association with cutaneous GVHD in human remains to be established. Methods. In the present study, Fas involvement in skin damage was assessed using a human skin explant model of GVHD. Fas and FasL expression were measured by immunohistochemistry and blockade of Fas pathway was investigated using an antagonistic anti-human Fas monoclonal antibody. In addition, levels of soluble Fas (sFas) were determined in the serum of patients receiving allogeneic HSCT with and without GVHD. Results. The results showed that Fas up-regulation in the epithelium of human skin explants correlated with graft-versus-host reaction (GVHR) in the skin explant model (P<0.001). Decreased GVHR grades were observed by using a Fas blocking monoclonal antibody. Levels of sFas were increased post-HSCT (P<0.001) but rather than being associated with the severity of GVHD, sFas levels differed with the conditioning treatments the patients received before the HSCT. Conclusions. Higher GVHR grades were associated with increased Fas expression in the epithelium of the skin explants. In addition, by blocking Fas-mediated apoptosis, the GVHR grades were decreased. Our study thus shows the involvement of Fas in cutaneous GVHD damage, and supports the potential use of Fas as a therapeutic target.

Publication metadata

Author(s): Ruffin N, Ahmed SS, Osorio LM, Wang XN, Jackson GH, Collin MP, Ekre HP, Chiodi F, Dickinson AM

Publication type: Article

Publication status: Published

Journal: Transplantation

Year: 2011

Volume: 91

Issue: 9

Pages: 946-951

Print publication date: 01/05/2011

ISSN (print): 0041-1337

ISSN (electronic): 1534-6080

Publisher: Lippincott Williams & Wilkins

URL: http://dx.doi.org/10.1097/TP.0b013e318212c833

DOI: 10.1097/TP.0b013e318212c833

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