Expression profiling of major histocompatibility and natural killer complex genes reveals candidates for controlling risk of graft versus host disease.
Expression profiling of major histocompatibility and natural killer complex genes reveals candidates for controlling risk of graft versus host disease.
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DOI：
10.1371/journal.pone.0016582
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发表时间：
2011-01-28
期刊：
影响因子：
3.7
通讯作者：
Dressel R
中科院分区：
文献类型：
--
作者：
Novota P;Zinöcker S;Norden J;Wang XN;Sviland L;Opitz L;Salinas-Riester G;Rolstad B;Dickinson AM;Walter L;Dressel R
主要组织相容性复合体（MHC）是最重要的基因组区域，导致造血干细胞移植后发生移植物抗宿主病（GVHD）的风险。 MHC I 类和 II 类基因的匹配对于移植的成功至关重要。然而，MHC 包含的其他基因也会增加发生急性 GVHD 的风险。由于该区域的连锁不平衡，仅通过遗传关联研究很难识别这些基因。因此，我们的目的是通过 mRNA 表达谱来鉴定 MHC 基因和其他参与 GVHD 病理生理学的基因。为了降低任务的复杂性，我们使用遗传明确的大鼠近交系和大鼠皮肤外植体测定（移植物抗宿主反应（GVHR）的体外模型）来分析皮肤 GVHR 中 MHC、自然杀伤复合物（NKC）和其他基因的表达。我们观察到其他基因组区域编码的 11 个 MHC、6 个 NKC 和 168 个基因出现统计显着且强烈的上调或下调，即分别占测试基因的 4.9%、14.0% 和 2.6%。通过定量实时 PCR 和独立皮肤外植体测定证实了 7 个选定的 MHC 和 3 个 NKC 基因的调节。此外，在移植大鼠受 GVHD 影响的皮肤损伤和人类皮肤外植体测定中观察到大多数选定基因的类似调控。我们在皮肤外植体检测中鉴定了大鼠和人类 MHC 和 NKC 基因，这些基因在 GVHR 过程中受到调节，因此可以作为 GVHD 的生物标志物。一些人类基因，包括 HLA-DMB、C2、AIF1、SPR1、UBD 和 OLR1，都是多态性的。因此，这些候选者可能会增加患者发生 GVHD 的遗传风险。
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. 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. 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.
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通过供体基因表达分析对人类的移植物抗宿主疾病的预测。
影响因子：
15.8
作者：
Baron C;Somogyi R;Greller LD;Rineau V;Wilkinson P;Cho CR;Cameron MJ;Kelvin DJ;Chagnon P;Roy DC;Busque L;Sékaly RP;Perreault C
通讯作者：
Perreault C
影响因子：
4.8
作者：
Cao, XQ;Cismowski, MJ;Lanier, SM
通讯作者：
Lanier, SM
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
37.8
作者：
Chen, Q;Reis, SE;Kamboh, MI
通讯作者：
Kamboh, MI
影响因子：
3.3
作者：
Buzzeo, Matthew P.;Yang, Jie;Reddy, Vijay
通讯作者：
Reddy, Vijay