title: Expression profiling of major histocompatibility and natural killer complex genes reveals candidates for controlling risk of graft versus host disease.
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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Cellular and Molecular Immunology, University of Göttingen, Göttingen, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Novota
authors.forename: Severin
authors.initials: S
authors.lastname: Zinöcker
authors.forename: Jean
authors.initials: J
authors.lastname: Norden
authors.forename: Xiao Nong
authors.initials: XN
authors.lastname: Wang
authors.forename: Lisbet
authors.initials: L
authors.lastname: Sviland
authors.forename: Lennart
authors.initials: L
authors.lastname: Opitz
authors.forename: Gabriela
authors.initials: G
authors.lastname: Salinas-Riester
authors.forename: Bent
authors.initials: B
authors.lastname: Rolstad
authors.forename: Anne M
authors.initials: AM
authors.lastname: Dickinson
authors.forename: Lutz
authors.initials: L
authors.lastname: Walter
authors.forename: Ralf
authors.initials: R
authors.lastname: Dressel
mesh_terms: D000818:Animals; D015415:Biomarkers; D020869:Gene Expression Profiling; D006086:Graft vs Host Disease / Q000235:genetics / Q000517:prevention & control*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D055607:Receptors, Natural Killer Cell / Q000235:genetics*; D012306:Risk; D012871:Skin Diseases
chemical_list: D015415:Biomarkers; D055607:Receptors, Natural Killer Cell