PDF(Pubmed)
Abstract：
Fever has a complicated etiology, and diagnosing its causative factor is clinically challenging. Human cytomegalovirus (HCMV) infection causes various diseases. However, the clinical relevance, prevalence, and significance of HCMV microRNAs (miRNA) in association with fever remain unclear. In the present study, we analyzed the HCMV miRNA expression pattern in the serum of patients with fever and evaluate its clinical associations with occult HCMV infection status in immune disorders.
We included serum samples from 138 patients with fever and 151 age-gender-matched controls in this study. First, the serum levels of 24 HCMV miRNAs were determined using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in the training set. The markedly altered miRNAs were verified in the validation and testing sets. The serum HCMV IgG/IgM and DNA titers in the testing cohort were also assessed using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR, respectively.
The majority of HCMV miRNAs were markedly upregulated in the serum of fever patients. We selected the five most significantly altered HCMV miRNAs: hcmv-miR-US4-3p, hcmv-miR-US29-3p, hcmv-miR-US5-2-3p, hcmv-miR-UL112-3p, and hcmv-miR-US33-3p for validation. These miRNAs were also significantly elevated in the serum of fever patients in the validation and testing sets compared with the controls. Logistic regression analysis revealed that the five miRNAs were novel potential risk factors for fever. Notably, the serum levels of four of the five confirmed HCMV miRNAs were significantly associated with blood C-reaction protein concentrations. Moreover, the five HCMV miRNA levels were closely correlated with the HCMV DNA titers in the testing cohort.
HCMV infection and activation are common in fever patients and could be novel risk factors for fever. These differentially expressed HCMV miRNAs could enable HCMV activation status monitoring in immune disorders.
We included serum samples from 138 patients with fever and 151 age-gender-matched controls in this study. First, the serum levels of 24 HCMV miRNAs were determined using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in the training set. The markedly altered miRNAs were verified in the validation and testing sets. The serum HCMV IgG/IgM and DNA titers in the testing cohort were also assessed using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR, respectively.
The majority of HCMV miRNAs were markedly upregulated in the serum of fever patients. We selected the five most significantly altered HCMV miRNAs: hcmv-miR-US4-3p, hcmv-miR-US29-3p, hcmv-miR-US5-2-3p, hcmv-miR-UL112-3p, and hcmv-miR-US33-3p for validation. These miRNAs were also significantly elevated in the serum of fever patients in the validation and testing sets compared with the controls. Logistic regression analysis revealed that the five miRNAs were novel potential risk factors for fever. Notably, the serum levels of four of the five confirmed HCMV miRNAs were significantly associated with blood C-reaction protein concentrations. Moreover, the five HCMV miRNA levels were closely correlated with the HCMV DNA titers in the testing cohort.
HCMV infection and activation are common in fever patients and could be novel risk factors for fever. These differentially expressed HCMV miRNAs could enable HCMV activation status monitoring in immune disorders.
摘要：
未经证实：发热的病因复杂，诊断其致病因素在临床上具有挑战性。人巨细胞病毒(HCMV)感染可引起多种疾病。然而,临床相关性，患病率,HCMV微小RNA（miRNA）与发热相关的意义尚不清楚。在本研究中,我们分析了发热患者血清中HCMVmiRNA的表达模式，并评估了其与免疫疾病中隐匿性HCMV感染状态的临床关联。
UNASSIGNED：我们纳入了138例发热患者和151例年龄性别匹配对照的血清样本。首先,在训练集中使用基于水解探针的茎环定量逆转录聚合酶链反应(RT-qPCR)测定24种HCMVmiRNA的血清水平.在验证和测试集中验证了显著改变的miRNA。还使用酶联免疫吸附测定（ELISA）和RT-qPCR评估了测试队列中的血清HCMVIgG/IgM和DNA滴度，分别。
未经证实：大多数HCMVmiRNAs在发热患者血清中显著上调。我们选择了五个最显著改变的HCMVmiRNA：hcmv-miR-US4-3p，hcmv-miR-US29-3p,hcmv-miR-US5-2-3p,hcmv-miR-UL112-3p,和hcmv-miR-US33-3p进行验证。与对照相比,这些miRNA在验证和测试组中的发热患者的血清中也显著升高。Logistic回归分析显示,5种miRNAs是发热的潜在危险因素。值得注意的是,5种确认的HCMVmiRNAs中4种的血清水平与血液C反应蛋白浓度显著相关.此外，在测试队列中,5个HCMVmiRNA水平与HCMVDNA滴度密切相关.
未经证实：HCMV感染和激活在发热患者中很常见，可能是发热的新危险因素。这些差异表达的HCMVmiRNA可以使得能够监测免疫病症中的HCMV活化状态。
UNASSIGNED：我们纳入了138例发热患者和151例年龄性别匹配对照的血清样本。首先,在训练集中使用基于水解探针的茎环定量逆转录聚合酶链反应(RT-qPCR)测定24种HCMVmiRNA的血清水平.在验证和测试集中验证了显著改变的miRNA。还使用酶联免疫吸附测定（ELISA）和RT-qPCR评估了测试队列中的血清HCMVIgG/IgM和DNA滴度，分别。
未经证实：大多数HCMVmiRNAs在发热患者血清中显著上调。我们选择了五个最显著改变的HCMVmiRNA：hcmv-miR-US4-3p，hcmv-miR-US29-3p,hcmv-miR-US5-2-3p,hcmv-miR-UL112-3p,和hcmv-miR-US33-3p进行验证。与对照相比,这些miRNA在验证和测试组中的发热患者的血清中也显著升高。Logistic回归分析显示,5种miRNAs是发热的潜在危险因素。值得注意的是,5种确认的HCMVmiRNAs中4种的血清水平与血液C反应蛋白浓度显著相关.此外，在测试队列中,5个HCMVmiRNA水平与HCMVDNA滴度密切相关.
未经证实：HCMV感染和激活在发热患者中很常见，可能是发热的新危险因素。这些差异表达的HCMVmiRNA可以使得能够监测免疫病症中的HCMV活化状态。
