PDF(Pubmed)
Abstract：
BACKGROUND: Humoral memory and specific antibody levels depend on the kind of antigen and individual immunofactors. The presence of IgM antibodies or a fourfold rise in specific IgG levels are generally accepted as diagnostic factors in the serology of acute viral infections. This basic model is not adequate for the herpes virome, especially after hematopoietic stem cell transplantation (HSCT), due to continuous, usually multifocal antigenic stimulation, various donor serostatuses, immunosuppression, and individual immunoreconstitution.
METHODS: A case-control study was conducted to identify active infection cases of human herpesvirus (HHV) (from 300 diagnosed immunocompromised patients) and to evaluate historically associated humoral factors to look at outcomes. We considered only the data of patients with meticulous differential diagnosis to exclude other causes, and thereby to observe pathways and temporal relationships, not the statistical ones usually collected in cohorts. Despite the small number, such data collection and analysis methods avoid a number of biases and indicate cause and effect.
RESULTS: In this observational study, a retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation showed a number of biases. Two well-differentiated cases (confirmed by a Tzanck test) with various diseases and conditioning evolutions of immune parameters showed an interesting pathway. Exponential decreases in specific IgGs after HSCT preceded virus replication were observed, with a cytopathic effect (shingles, VZV encephalitis and HSV-induced mucositis). The minima (lowest IgG levels) before herpesvirus reactivation were 234.23 mIU/mL and 94 RU/mL for VZV and HSV, respectively. This coincided with a low CD4 titer, but without other infectious processes. Other immune response parameters such as Treg, cytotoxic T cells, and complement and total IgG level were the same as they were before the transplant procedure. Interestingly, a second wave of immunoreconstitution with an anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. A patient with lymphocyte depletion in conditioning showed an earlier second wave of immunoreconstitution (6th vs. 14th month).
CONCLUSIONS: As is typical for infancy, the kinetics of the IgG level is unique after HSCT (the decline phase is first). Host microbiome factors (e.g., HHV1-3-serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help in predicting prognoses and improve disease management. A lack of differentiation and the confusing bias of the assessor (i.e., observer selection bias) are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be the first to build evidence of a pathway and an association between immune parameters and HHV disease.
METHODS: A case-control study was conducted to identify active infection cases of human herpesvirus (HHV) (from 300 diagnosed immunocompromised patients) and to evaluate historically associated humoral factors to look at outcomes. We considered only the data of patients with meticulous differential diagnosis to exclude other causes, and thereby to observe pathways and temporal relationships, not the statistical ones usually collected in cohorts. Despite the small number, such data collection and analysis methods avoid a number of biases and indicate cause and effect.
RESULTS: In this observational study, a retrospective analysis of data from 300 patients with clinical diagnosis of herpes simplex virus (HSV) and varicella zoster virus (VZV) reactivation showed a number of biases. Two well-differentiated cases (confirmed by a Tzanck test) with various diseases and conditioning evolutions of immune parameters showed an interesting pathway. Exponential decreases in specific IgGs after HSCT preceded virus replication were observed, with a cytopathic effect (shingles, VZV encephalitis and HSV-induced mucositis). The minima (lowest IgG levels) before herpesvirus reactivation were 234.23 mIU/mL and 94 RU/mL for VZV and HSV, respectively. This coincided with a low CD4 titer, but without other infectious processes. Other immune response parameters such as Treg, cytotoxic T cells, and complement and total IgG level were the same as they were before the transplant procedure. Interestingly, a second wave of immunoreconstitution with an anamnestic antibody response was not always observed. It coincided with prolonged herpes viral infection. A patient with lymphocyte depletion in conditioning showed an earlier second wave of immunoreconstitution (6th vs. 14th month).
CONCLUSIONS: As is typical for infancy, the kinetics of the IgG level is unique after HSCT (the decline phase is first). Host microbiome factors (e.g., HHV1-3-serostatus) should be taken into account to predict risk of non-relapse mortality and survival after HSCT. The levels of specific antibodies help in predicting prognoses and improve disease management. A lack of differentiation and the confusing bias of the assessor (i.e., observer selection bias) are the main obstacles in statistical HHV1-3 research. Such time-lapse case studies may be the first to build evidence of a pathway and an association between immune parameters and HHV disease.
摘要：
背景：体液记忆和特异性抗体水平取决于抗原的种类和个体免疫因子。IgM抗体的存在或特异性IgG水平升高四倍通常被认为是急性病毒感染血清学中的诊断因素。这个基本模型对疱疹病毒来说是不够的，尤其是造血干细胞移植（HSCT）后，由于连续,通常是多灶性抗原刺激，各种供体血清，免疫抑制,和个体免疫重建。
方法：进行了一项病例对照研究，以确定人类疱疹病毒（HHV）的活动性感染病例（来自300例确诊的免疫功能低下患者），并评估历史相关的体液因素以观察结果。我们仅考虑经过细致鉴别诊断的患者数据，以排除其他原因，从而观察路径和时间关系，不是通常在队列中收集的统计信息。尽管数量少,这种数据收集和分析方法避免了一些偏见，并指出了因果关系。
结果：在这项观察性研究中，对临床诊断为单纯疱疹病毒(HSV)和水痘带状疱疹病毒(VZV)再激活的300例患者的数据进行的回顾性分析显示存在许多偏差.具有各种疾病和免疫参数的条件演变的两个分化良好的病例（通过Tzanck测试证实）显示出有趣的途径。观察到HSCT在病毒复制之前特异性IgG的指数减少，具有细胞病变效应(带状疱疹，VZV脑炎和HSV引起的粘膜炎）。对于VZV和HSV，疱疹病毒再激活前的最小值（最低IgG水平）为234.23mIU/mL和94RU/mL，分别。这与低CD4滴度相吻合，但没有其他感染过程。其他免疫应答参数如Treg、细胞毒性T细胞，补体和总IgG水平与移植前相同。有趣的是,并不总是观察到第二波免疫重建与记忆抗体反应。它与长期的疱疹病毒感染相吻合。在调理中淋巴细胞耗竭的患者显示出更早的第二波免疫重建（第6与14个月）。
结论：对于婴儿期，HSCT后IgG水平的动力学是独特的（下降阶段是第一）。宿主微生物组因子(例如，应考虑HHV1-3-血清状态）以预测HSCT后非复发死亡率和生存率的风险。特异性抗体的水平有助于预测预后和改善疾病管理。缺乏差异化和评估者令人困惑的偏见(即，观察者选择偏差)是统计HHV1-3研究的主要障碍。这种延时案例研究可能是第一个建立途径和免疫参数与HHV疾病之间关联的证据。
方法：进行了一项病例对照研究，以确定人类疱疹病毒（HHV）的活动性感染病例（来自300例确诊的免疫功能低下患者），并评估历史相关的体液因素以观察结果。我们仅考虑经过细致鉴别诊断的患者数据，以排除其他原因，从而观察路径和时间关系，不是通常在队列中收集的统计信息。尽管数量少,这种数据收集和分析方法避免了一些偏见，并指出了因果关系。
结果：在这项观察性研究中，对临床诊断为单纯疱疹病毒(HSV)和水痘带状疱疹病毒(VZV)再激活的300例患者的数据进行的回顾性分析显示存在许多偏差.具有各种疾病和免疫参数的条件演变的两个分化良好的病例（通过Tzanck测试证实）显示出有趣的途径。观察到HSCT在病毒复制之前特异性IgG的指数减少，具有细胞病变效应(带状疱疹，VZV脑炎和HSV引起的粘膜炎）。对于VZV和HSV，疱疹病毒再激活前的最小值（最低IgG水平）为234.23mIU/mL和94RU/mL，分别。这与低CD4滴度相吻合，但没有其他感染过程。其他免疫应答参数如Treg、细胞毒性T细胞，补体和总IgG水平与移植前相同。有趣的是,并不总是观察到第二波免疫重建与记忆抗体反应。它与长期的疱疹病毒感染相吻合。在调理中淋巴细胞耗竭的患者显示出更早的第二波免疫重建（第6与14个月）。
结论：对于婴儿期，HSCT后IgG水平的动力学是独特的（下降阶段是第一）。宿主微生物组因子(例如，应考虑HHV1-3-血清状态）以预测HSCT后非复发死亡率和生存率的风险。特异性抗体的水平有助于预测预后和改善疾病管理。缺乏差异化和评估者令人困惑的偏见(即，观察者选择偏差)是统计HHV1-3研究的主要障碍。这种延时案例研究可能是第一个建立途径和免疫参数与HHV疾病之间关联的证据。
