Correlation of Hsp70-1 and Hsp70-2 gene expression with the degree of graft-versus-host reaction in a rat skin explant model.
BACKGROUND
Graft-versus-host disease (GVHD) is the most serious complication after allogeneic hematopoietic stem-cell transplantation. A human skin explant assay has been used to predict the risk of GVHD in patients by histological grading of graft-versus-host reactions (GVHR). New molecular markers of GVHR might help to further increase the predictive value of the assay.


METHODS
A rat skin explant assay has been developed to further aid in identifying potential novel molecular markers.


RESULTS
In inbred rat strains GVHR were observed in skin explants co-cultured with allogeneic lymphocytes stimulated against minor or major histocompatibility antigens. The histological signs of GVHR were similar to those observed in human skin explant assays and acute GVHD lesions occurring in rats after experimental bone marrow transplantation. Heat shock protein (HSP) 70 has been shown to be expressed during GVHR. We therefore investigated the expression of the three major histocompatibility complex (MHC)-linked HSP70 genes in rat skin explants. The two major stress-inducible genes Hsp70-1 and Hsp70-2 were found to be upregulated in the allogeneic rat skin explant assays. The increase in mRNA correlated with the GVHR grade (I-IV). Interestingly, the expression of the third MHC-linked Hsp70 gene Hsp70-3 was not found to be augmented during GVHR.


CONCLUSIONS
The observed induction of the MHC-encoded Hsp70-1 and Hsp70-2 genes might serve as new markers of GVHR and as potentially novel diagnostic tools for GVHD.
Novota
Peter
P
Department of Cellular and Molecular Immunology, University of Göttingen, Göttingen, Germany.
Sviland
Lisbet
L
Zinöcker
Severin
S
Stocki
Pawel
P
Balavarca
Yesilda
Y
Bickeböller
Heike
H
Rolstad
Bent
B
Wang
Xiao N
XN
Dickinson
Anne M
AM
Dressel
Ralf
R
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016026:Bone Marrow Transplantation / Q000276:immunology; D004195:Disease Models, Animal; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism; D006087:Graft vs Host Reaction / Q000276:immunology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D050884:HSP72 Heat-Shock Proteins / Q000378:metabolism*; D008285:Major Histocompatibility Complex / Q000276:immunology; D015778:Minor Histocompatibility Antigens / Q000276:immunology; D023421:Models, Animal; D011237:Predictive Value of Tests; D051381:Rats; D011917:Rats, Inbred Lew; D012867:Skin / Q000276:immunology; D016038:Skin Transplantation / Q000276:immunology*; D014181:Transplantation Immunology
D015415:Biomarkers; D018840:HSP70 Heat-Shock Proteins; D050884:HSP72 Heat-Shock Proteins; C490435:Hspa2 protein, rat; D015778:Minor Histocompatibility Antigens