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Analysis of the pathogenesis of acute GVHD like illness caused by HHV-6 infection after hematopoietic stem cell transplantation

造血干细胞移植后HHV-6感染引起急性GVHD样疾病发病机制分析

基本信息

批准号：
14570740
负责人：
YOSHIKAWA Tetsushi
金额：
$ 2.24万
依托单位：
Fujita Health University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570740/
关键词：
HHV-6 SCT acute GVHD cytokine RNA real-time PCR 造血幹細胞移植サイトカイン SCT cytokines RNA HHV-7 BMT reactivation skin rash

项目摘要

Although it has been demonstrated that human herpesvirus 6 (HHV-6) infection occurs almost half of the hematopoietic stem cell transplant (HSCT) recipients, and might be associated with several clinical manifestations including acute graft versus host disease, mechanisms of viral reactivation remains unclear. To explore the mechanisms of HHV-6 reactivation in HSCT recipients, we sequentially monitored serum proinflamatory cytokines (IL-G, TNF-α, and IL-1β) levels and HHV-6 infection (viral isolation and serological assay) in the 24 pediatric patients after HSCT. Of the patients, 14 (58.3%) developed HHV-6 infection, and 9 (37.5%) developed HHV-6 viremia around 2 weeks (days 0, 14, 15, 14, 16, 15, 13, 21, and 22) after transplantation. The mean levels of three cytokines (IL-6, TNF-α, and IL-1β), which were measured at days 0, 7, 14, and 28 of post-transplant, were compared between patients with HHV-6 infection and those without HHV-6 infection. IL-6 levels were significantly higher in patients with HHV-6 infection than in those without HHV-6 infection at day 7 (54.8 vs 16.3 pg/ml; P=0.0272), 14 (44.2 vs 0.4 pg/ml; P=0.0002), and 28 (18.8 vs 4.4 pg/ml; P=0.0137). In addition, TNF-α level was significantly higher in patients with HHV-6 infection than in those without HHV-6 infection at day 14 (13.1 vs 3; P= 0.023). In other time points, there was no significant difference of mean IL-6 and TNF-α levels between. patients with HHV-6 infection and those without HHV-6 infection. Low level of IL-16 was detected in small number of serum samples, and there was no significant difference between patients with HHV-6 infection and those without HHN-6 infection. These results suggest that proinflamatory cytokines, in particular IL-6 and TNF-α, may play an important role in the pathogenesis of HHV-6 infection after HSCT, and may be a useful predictor for HHV-6 :infection.

尽管已证实人类疱疹病毒6型(HHV-6)感染几乎发生在一半的造血干细胞移植(HSCT)受者身上，并可能与包括急性移植物抗宿主病在内的几种临床表现有关，但病毒重新激活的机制尚不清楚。为探讨异基因造血干细胞移植后HHV-6重新激活的机制，我们对24例接受HSCT的儿童患者进行了血清促炎症细胞因子(IL-G、肿瘤坏死因子-α和IL-1β)水平和HHV-6感染(病毒分离和血清学检测)的动态监测。在移植后2周(0、14、15、14、16、15、13、21、22天)，14例(58.3%)患者出现HHV-6感染，9例(37.5%)出现HHV-6病毒血症。分别于移植后第0、7、14、28天检测HHV-6感染者和非HHV-6感染者血清中IL-6、肿瘤坏死因子-α和IL-1β的平均水平。HHV-6感染者IL-6水平在第7天(54.8pg/ml对16.3pg/ml；P=0.0272)、第14天(44.2pg/ml对0.4pg/ml；P=0.0002)和28天(18.8pg/ml对4.4pg/ml；P=0.0137)显著高于未感染HHV-6者。此外，感染HHV-6的患者第14天的肿瘤坏死因子-α水平显著高于未感染的患者(13.1vs3；P=0.023)。在其他时间点，IL-6和肿瘤坏死因子-α的平均水平在两组间无显著差异。HHV-6感染患者和未感染HHV-6患者。在少数血清标本中检测到低水平的IL-16，HHV-6感染者与未感染HHN-6病人之间无显著差异。提示促炎症细胞因子，尤其是IL-6和肿瘤坏死因子-α可能在造血干细胞移植后HHV-6感染的发病机制中起重要作用，并可作为预测HHV-6感染的有用指标。