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dc.contributor.authorNovota, Petereng
dc.contributor.authorZinöcker, Severineng
dc.contributor.authorNorden, Jeaneng
dc.contributor.authorWang, Xiao Nongeng
dc.contributor.authorSviland, Lisbeteng
dc.contributor.authorOpitz, Lennarteng
dc.contributor.authorSalinas-Riester, Gabrielaeng
dc.contributor.authorRolstad, Benteng
dc.contributor.authorDickinson, Anne M.eng
dc.contributor.authorWalter, Lutzeng
dc.contributor.authorDressel, Ralfeng
dc.date.accessioned2011-12-09T13:11:30Z
dc.date.available2011-12-09T13:11:30Z
dc.date.issued2011-01-28eng
dc.identifier.citationPLoS ONE 6(1): e16582en
dc.identifier.issn1932-6203eng
dc.identifier.urihttp://hdl.handle.net/1956/5275
dc.description.abstractBackground: The major histocompatibility complex (MHC) is the most important genomic region that contributes to the risk of graft versus host disease (GVHD) after haematopoietic stem cell transplantation. Matching of MHC class I and II genes is essential for the success of transplantation. However, the MHC contains additional genes that also contribute to the risk of developing acute GVHD. It is difficult to identify these genes by genetic association studies alone due to linkage disequilibrium in this region. Therefore, we aimed to identify MHC genes and other genes involved in the pathophysiology of GVHD by mRNA expression profiling. Methodology/Principal Findings: To reduce the complexity of the task, we used genetically well-defined rat inbred strains and a rat skin explant assay, an in-vitro-model of the graft versus host reaction (GVHR), to analyze the expression of MHC, natural killer complex (NKC), and other genes in cutaneous GVHR. We observed a statistically significant and strong up or down regulation of 11 MHC, 6 NKC, and 168 genes encoded in other genomic regions, i.e. 4.9%, 14.0%, and 2.6% of the tested genes respectively. The regulation of 7 selected MHC and 3 NKC genes was confirmed by quantitative real-time PCR and in independent skin explant assays. In addition, similar regulations of most of the selected genes were observed in GVHD-affected skin lesions of transplanted rats and in human skin explant assays. Conclusions/Significance: We identified rat and human MHC and NKC genes that are regulated during GVHR in skin explant assays and could therefore serve as biomarkers for GVHD. Several of the respective human genes, including HLA-DMB, C2, AIF1, SPR1, UBD, and OLR1, are polymorphic. These candidates may therefore contribute to the genetic risk of GVHD in patients.en
dc.language.isoengeng
dc.publisherPublic Library of Scienceeng
dc.titleExpression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Diseaseeng
dc.typePeer reviewedeng
dc.typeJournal articleeng
dc.subject.nsiVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714eng
dc.rights.holderCopyright 2011 Novota et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
dc.type.versionpublishedVersioneng
bora.peerreviewedPeer reviewedeng
bibo.doihttp://dx.doi.org/10.1371/journal.pone.0016582eng
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0016582


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