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Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease

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dc.contributor.author Novota, Peter
dc.contributor.author Zinöcker, Severin
dc.contributor.author Norden, Jean
dc.contributor.author Wang, Xiao Nong
dc.contributor.author Sviland, Lisbet
dc.contributor.author Opitz, Lennart
dc.contributor.author Salinas-Riester, Gabriela
dc.contributor.author Rolstad, Bent
dc.contributor.author Dickinson, Anne M.
dc.contributor.author Walter, Lutz
dc.contributor.author Dressel, Ralf
dc.date.accessioned 2011-12-09T13:11:30Z
dc.date.available 2011-12-09T13:11:30Z
dc.date.issued 2011-01-28
dc.identifier.citation PLoS ONE 6(1): e16582 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://dx.doi.org/10.1371/journal.pone.0016582
dc.identifier.uri http://hdl.handle.net/1956/5275
dc.description.abstract Background: 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.iso eng en
dc.publisher Public Library of Science en
dc.rights Copyright 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. en
dc.title Expression Profiling of Major Histocompatibility and Natural Killer Complex Genes Reveals Candidates for Controlling Risk of Graft versus Host Disease en
dc.type Peer reviewed en
dc.type Journal article en
dc.subject.nsi VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical genetics: 714 en
dc.type.version publishedVersion en


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