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[阿尔茨海默病不同阶段患者的疱疹病毒感染与免疫紊乱]

[Herpesvirus infections and immunological disturbances in patients with different stages of Alzheimer's disease].

作者信息

Krynskiy S A, Malashenkova I K, Ogurtsov D P, Khailov N A, Chekulaeva E I, Shipulina O Y, Ponomareva E V, Gavrilova S I, Didkovsky N A, Velichkovsky B M

机构信息

NRC «Kurchatov Institute».

NRC «Kurchatov Institute»; FSBI «Federal Scientific and Clinical Center for Physico-Chemical Medicine of the Federal Medical and Biological Agency».

出版信息

Vopr Virusol. 2021 May 15;66(2):129-139. doi: 10.36233/0507-4088-32.

Abstract

INTRODUCTION

Alzheimer's disease (AD) is a multifactorial disease that leads to a progressive memory loss, visualspatial impairments, emotional and personality changes. As its earliest pre-dementia clinical stage, amnestic mild cognitive impairment syndrome (aMCI) is currently considered. Neuroinflammation plays a role in the development and progression of aMCI and the initial stage of AD, which can be supported by immunological disorders of a systemic character. Study of factors, including infections, influencing immune disorders and systemic inflammatory response in patients with aMCI, is of great importance.The aim of this study was to obtain new data on the possible role of herpesvirus infections in the development and progression of aMCI.

MATERIAL AND METHODS

100 patients with aMCI diagnosis, 45 patients with AD, 40 people from the control group were enrolled into the study. The frequency of DNA detection of herpesviruses (Epstein-Barr virus (EBV), human herpesviruses (HHV) type 6 and 7, cytomegalovirus (CMV)), the levels of viral load and the serological markers of herpesvirus infections (IgG to HHV-1, IgG to CMV) were determined. Immunological studies included an assessment of the level of the main pro-inflammatory and anti-inflammatory cytokines, and indicators of humoral and cellular immunity.

RESULTS

The study found an increased detection rate of EBV in saliva and a higher level of EBV DNA in saliva in aMCI and AD than in the control group. A relationship between the presence of active EBV infection and changes in immunological parameters in patients with aMCI were found. It was also discovered that the level of IgG antibodies to CMV is associated with the stage of AD.

DISCUSSION

The results indicate a possible role of EBV- and CMV-induced infections in the development of immunological changes which are typical for mild cognitive impairment and in the progression of AD.

CONCLUSION

The obtained data can be important for prognostic methods addressing AD development, including its pre-dementia stage, and for new approaches to individualized treatment and prevention.

摘要

引言

阿尔茨海默病(AD)是一种多因素疾病,会导致进行性记忆丧失、视觉空间障碍、情绪和性格改变。作为其最早的痴呆前临床阶段,目前考虑遗忘型轻度认知障碍综合征(aMCI)。神经炎症在aMCI的发展和进展以及AD的初始阶段起作用,这可以由全身性免疫紊乱来支持。研究包括感染在内的影响aMCI患者免疫紊乱和全身炎症反应的因素非常重要。本研究的目的是获得关于疱疹病毒感染在aMCI发展和进展中可能作用的新数据。

材料与方法

100例诊断为aMCI的患者、45例AD患者、40名对照组人员纳入研究。测定疱疹病毒(爱泼斯坦-巴尔病毒(EBV)、人类疱疹病毒(HHV)6型和7型、巨细胞病毒(CMV))DNA检测频率、病毒载量水平以及疱疹病毒感染的血清学标志物(抗HHV-1 IgG、抗CMV IgG)。免疫研究包括评估主要促炎和抗炎细胞因子水平以及体液和细胞免疫指标。

结果

研究发现,aMCI和AD患者唾液中EBV的检测率增加,且唾液中EBV DNA水平高于对照组。发现aMCI患者中活动性EBV感染的存在与免疫参数变化之间存在关联。还发现抗CMV IgG抗体水平与AD阶段相关。

讨论

结果表明,EBV和CMV诱导的感染可能在轻度认知障碍典型的免疫变化发展以及AD进展中起作用。

结论

所获得的数据对于针对AD发展(包括其痴呆前阶段)的预后方法以及个性化治疗和预防的新方法可能具有重要意义。

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