PDF(Pubmed)
Abstract：
Herpes zoster, which is due to the reactivation of Varicella zoster virus (VZV), is a leading cause of morbidity after allogeneic hematopoietic stem cell transplantation (allo-HSCT). While cell-mediated immunity (CMI) is critical to inhibiting VZV reactivation, CMI is not routinely assessed due to a lack of reliable tests. In this study, we aimed to evaluate VZV-specific CMI among allo-HSCT recipients (n = 60) and healthy individuals (HI, n = 17) through a panel of three immune functional assays after ex vivo stimulation by VZV antigen: quantification of (i) IFN-γ release in the supernatants, (ii) T-cell proliferation after a 7-day stimulation of peripheral blood mononuclear cells (PBMC), and (iii) measurement of the ifn-γ mRNA gene expression level after 24 h of stimulation of a whole-blood sample. VZV responsiveness was defined according to IFN-γ release from VZV-stimulated PBMC. Upon VZV stimulation, we found that allo-HSCT recipients at a median time of 6 [5-8] months post-transplant had lower IFN-γ release (median [IQR], 0.34 [0.12-8.56] vs. 409.5 [143.9-910.2] pg/ml, P <.0001) and fewer proliferating T cells (0.05 [0.01-0.57] % vs. 8.74 [3.12-15.05] %, P <.0001) than HI. A subset of allo-HSCT recipients (VZV-responders, n = 15/57, 26%) distinguished themselves from VZV-non-responders (n = 42/57, 74%; missing data, n = 3) by higher IFN-γ release (80.45 [54.3-312.8] vs. 0.22 [0.12-0.42] pg/ml, P <.0001) and T-cell proliferation (2.22 [1.18-7.56] % vs. 0.002 [0.001-0.11] %, P <.0001), suggesting recovery of VZV-specific CMI. Interestingly, VZV responders had a significant fold increase in ifn-γ gene expression, whereas ifn-γ mRNA was not detected in whole blood of VZV-non-responders (P <.0001). This study is the first to suggest that measurement of ifn-γ gene expression in 24-h-stimulated whole blood could be an accurate test of VZV-specific CMI. The routine use of this immune functional assay to guide antiviral prophylaxis at an individual level remains to be evaluated.
摘要：
带状疱疹,这是由于水痘带状疱疹病毒（VZV）的重新激活，是异基因造血干细胞移植（allo-HSCT）后发病的主要原因。虽然细胞介导的免疫（CMI）对抑制VZV再激活至关重要，由于缺乏可靠的测试，CMI未进行常规评估。在这项研究中,我们旨在评估allo-HSCT接受者(n=60)和健康个体(HI，n=17）通过VZV抗原离体刺激后的一组三种免疫功能测定：定量（i）上清液中IFN-γ的释放，（ii）刺激外周血单核细胞（PBMC）7天后的T细胞增殖，和（iii）在刺激全血样品24小时后测量ifn-γmRNA基因表达水平。根据来自VZV刺激的PBMC的IFN-γ释放来定义VZV响应性。在VZV刺激下,我们发现，在移植后6[5-8]个月的中位时间，allo-HSCT接受者的IFN-γ释放较低（中位数[IQR]，0.34[0.12-8.56]vs.409.5[143.9-910.2]pg/ml，P<.0001）和较少的增殖T细胞（0.05[0.01-0.57]％vs.8.74[3.12-15.05]%,P<.0001）比HI。allo-HSCT接受者的子集(VZV应答者，n=15/57，26％）与VZV无反应者（n=42/57，74％；缺少数据，n=3）通过较高的IFN-γ释放（80.45[54.3-312.8]与0.22[0.12-0.42]pg/ml，P<.0001）和T细胞增殖（2.22[1.18-7.56]％vs.0.002[0.001-0.11]%,P<.0001),提示VZV特异性CMI的恢复。有趣的是,VZV应答者在ifn-γ基因表达上有显著的倍数增加，而在VZV无应答者的全血中未检测到ifn-γmRNA（P<.0001）。这项研究首次表明，在24小时刺激的全血中测量ifn-γ基因表达可能是VZV特异性CMI的准确测试。该免疫功能测定在个体水平上指导抗病毒预防的常规使用仍有待评估。
