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

虽然已经证明人类疱疹病毒6 （HHV-6）感染发生在造血干细胞移植（HSCT）受体的近一半，并且可能与几种临床表现相关，包括急性移植物抗宿主病，但病毒再激活的机制尚不清楚。为了探索HHV-6在HSCT受体中再激活的机制，我们对24例儿童HSCT后的血清促炎细胞因子（IL-G、TNF-α和IL-1β）水平和HHV-6感染（病毒分离和血清学检测）进行了顺序监测。其中14例（58.3%）发生HHV-6感染，9例（37.5%）在移植后2周（0、14、15、14、16、15、13、21和22天）发生HHV-6病毒血症。比较HHV-6感染和未感染患者移植后0、7、14和28天的三种细胞因子（IL-6、TNF-α和IL-1β）的平均水平。在第7天，HHV-6感染患者的IL-6水平显著高于未感染的患者（54.8 vs 16.3 pg/ml， P=0.0272）， 14 （44.2 vs 0.4 pg/ml， P=0.0002）和28 （18.8 vs 4.4 pg/ml， P=0.0137）。此外，在第14天，HHV-6感染患者的TNF-α水平显著高于未感染的患者（13.1 vs 3； P= 0.023）。在其他时间点，两组患者IL-6、TNF-α水平差异无统计学意义。HHV-6感染和未感染的患者。少量血清样本检测到低水平IL-16， HHV-6感染患者与未感染患者之间无显著差异。这些结果表明，促炎细胞因子，特别是IL-6和TNF-α，可能在HSCT后HHV-6感染的发病机制中起重要作用，并且可能是HHV-6感染的有用预测因子。

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.