Expression of activating KIR2DS2 and KIR2DS4 genes after hematopoietic cell transplantation: relevance to cytomegalovirus infection.
Expression of activating KIR2DS2 and KIR2DS4 genes after hematopoietic cell transplantation: relevance to cytomegalovirus infection.
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DOI：
10.1016/j.bbmt.2011.04.008
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发表时间：
2011-11
期刊：
影响因子：
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通讯作者：
Zaia JA
中科院分区：
文献类型：
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作者：
Gallez-Hawkins GM;Franck AE;Li X;Thao L;Oki A;Gendzekhadze K;Dagis A;Palmer J;Nakamura R;Forman SJ;Senitzer D;Zaia JA
激活杀伤细胞免疫球蛋白样受体（aKIR）在预防巨细胞病毒（CMV）再激活中的重要作用先前已在造血细胞移植（HCT）中有所描述。更具体地说，供体基因型中存在多种aKIR以及至少存在KIR2DS2和KIR2DS4确定了一组巨细胞病毒再激活风险较低的造血细胞移植患者。然而，具有KIR保护基因型的患者仍会发生巨细胞病毒感染，并且有人提出这是否是由于KIR缺乏表达所致的问题。在本报告中，通过基于mRNA的定量聚合酶链反应（Q - PCR）测量了供体细胞和造血细胞移植受者细胞中KIR2DS2和2DS4基因的表达，并与巨细胞病毒再激活相关联进行了研究。在来自健康造血细胞移植供体的对照样本中，KIR2DS2和KIR2DS4表达的中位数范围较低，35%被视为无表达者。有趣的是，与移植前供体的表达相比，造血细胞移植后KIR2DS2和KIR2DS4的表达升高，并且在巨细胞病毒血症（V）的造血细胞移植受者中与非病毒血症（NV）的受者相比显著升高。供体的巨细胞病毒血清阳性与aKIR表达无关，并且具有KIR2DS2或KIR2DS4基因型的供体无表达并不能预测受者的巨细胞病毒再激活。在对包括供体类型（同胞或无关）、移植来源 - 骨髓（BM）或外周血干细胞（PB）以及急性移植物抗宿主病（GVHD）分级等其他移植因素进行控制后，发现KIR基因表达升高的回归分析结果与KIR2DS2和KIR2DS4均相关，巨细胞病毒再激活的风险增加了7倍。我们推测巨细胞病毒血症的造血细胞移植受者中aKIR表达升高要么与激活巨细胞病毒的因素巧合，要么是由巨细胞病毒或对这种巨细胞病毒感染再激活有反应的细胞过程所引发。
The important role of activating Killer Immunoglobulin-like Receptors (aKIR) in protecting against cytomegalovirus (CMV) reactivation has been described previously in hematopoietic cell transplantation (HCT). More specifically, the presence of multiple aKIR and the presence of at least KIR2DS2 and KIR2DS4 in the donor genotype identified a group of HCT patients that were at low risk for CMV reactivation. However, CMV infection still occurs in patients with KIR protective genotype and the question was raised as to whether this was due to the lack of KIR expression. In this report, the expression of KIR2DS2 and 2DS4 gene, as measured by mRNA-based Q-PCR both in the donor cells and in the HCT recipient cells was studied relative to CMV reactivation. In the control samples from healthy HCT donors, the median range of for KIR2DS2 and KIR2DS4 expression was low with 35% considered null-expressers. Interestingly, KIR2DS2 and KIR2DS4 expression was elevated after HCT when compared to donor expression prior to transplant, and significantly elevated in the CMV viremic (V) compared to non-viremic (NV) HCT recipients. CMV seropositivity of donors was not associated with aKIR expression, and donor null-expression in those with KIR2DS2 or KIR2DS4 genotype did not predict for CMV reactivation in the recipient. After controlling for other transplant factors that included donor type (sibling or unrelated), transplant source -bone marrow (BM) or peripheral blood stem cells (PB) and acute GVHD grade, the result of the regression analysis of elevated KIR gene expression was found to be associated for both KIR2DS2 and KIR2DS4, with seven fold increase in risk for CMV reactivation. We speculate that the elevated aKIR expression in CMV viremic HCT recipients is either coincidental with factors that activate CMV or is initiated by CMV or cellular processes responsive to such CMV infection reactivation.