Novota Peter, Sviland Lisbet, Zinöcker Severin, Stocki Pawel, Balavarca Yesilda, Bickeböller Heike, Rolstad Bent, Wang Xiao N, Dickinson Anne M, Dressel Ralf
Department of Cellular and Molecular Immunology, University of Göttingen, Göttingen, Germany.
Transplantation. 2008 Jun 27;85(12):1809-16. doi: 10.1097/TP.0b013e31817753f7.
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.
A rat skin explant assay has been developed to further aid in identifying potential novel molecular markers.
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.
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.
移植物抗宿主病（GVHD）是异基因造血干细胞移植后最严重的并发症。人类皮肤外植体试验已被用于通过移植物抗宿主反应（GVHR）的组织学分级来预测患者发生GVHD的风险。GVHR的新分子标志物可能有助于进一步提高该试验的预测价值。
已开发出一种大鼠皮肤外植体试验，以进一步帮助鉴定潜在的新型分子标志物。
在近交系大鼠品系中，在与针对次要或主要组织相容性抗原刺激的同种异体淋巴细胞共培养的皮肤外植体中观察到GVHR。GVHR的组织学表现与在人类皮肤外植体试验以及实验性骨髓移植后大鼠发生的急性GVHD病变中观察到的相似。热休克蛋白（HSP）70已被证明在GVHR期间表达。因此，我们研究了大鼠皮肤外植体中三个主要组织相容性复合体（MHC）连锁的HSP70基因的表达。发现两个主要的应激诱导基因Hsp70-1和Hsp70-2在同种异体大鼠皮肤外植体试验中上调。mRNA的增加与GVHR分级（I-IV）相关。有趣的是，未发现第三个MHC连锁的Hsp70基因Hsp70-3在GVHR期间表达增加。
观察到的MHC编码的Hsp70-1和Hsp70-2基因的诱导可能作为GVHR的新标志物以及GVHD潜在的新型诊断工具。
