HSV-1-Specific IgG Subclasses Distribution and Serum Neutralizing Activity in Alzheimer's Disease and in Mild Cognitive Impairment
HSV-1-Specific IgG Subclasses Distribution and Serum Neutralizing Activity in Alzheimer's Disease and in Mild Cognitive Impairment
复制标题
DOI：
10.3233/jad-170966
复制
发表时间：
2018-01-01
影响因子：
4
通讯作者：
Clerici, Mario
中科院分区：
文献类型：
--
作者：
Agostini, Simone;Mancuso, Roberta;Clerici, Mario
人类单纯疱疹病毒1型（HSV-1）感染被认为在阿尔茨海默病（AD）的发展中发挥作用。免疫球蛋白G（IgG）可中和HSV-1活性，但病毒可通过表达有效结合除IgG外所有IgG亚类Fc部分的受体来逃避IgG介导的免疫应答（3）。我们分析了HSV-1特异性IgG亚类和IgG介导的血清中和活性对HSV-1的诊断为AD或轻度认知功能障碍（MCI）的个人，比较结果与年龄匹配的健康对照（HC）。186名个体入组研究：67名AD、58名MCI和61名HC。通过ELISA测定血清中HSV-1 IgG滴度和亚类、中和抗体（NAb）滴度和补体C3浓度（抗体介导的效应子活性的关键组分）;在HSV-1感染的Vero细胞上进行IgG中和活性。结果显示，尽管HSV-1特异性IgG（1）、IgG（2）和IgG（4）滴度以及补体C3血清浓度在所有个体组中相当，但与AD相比，在MCI中更频繁地检测到IgG（3）（89（75%; p < 0.05）和HC（68%; p = 0.003），而三组之间滴度相似（AD：0.66 +/- 0.21 OD; MCI：0.68 +/- 0.24 OD; HC：0.72 +/- 0.28 OD）。值得注意的是，即使在存在大量IgG的情况下，AD血清的HSV-1特异性中和能力也降低（3）。由于IgG（3）在抵消HSV-1逃避免疫应答的能力中起关键作用，这些数据加强了HSV-1在AD中的致病作用的假设。
Human Herpes Simplex Virus type 1 (HSV-1) infection is suggested to play a role in the development of Alzheimer's disease (AD). Immunoglobulin G (IgG) neutralize HSV-1 activity, but the virus can evade IgG-mediated immune responses by expressing receptor that efficiently binds the Fc portion of all IgG subclasses with the exception of IgG(3). We analyzed HSV-1-specific IgG subclasses and IgG-mediated serum neutralization activity against HSV-1 in individuals with a diagnosis of either AD or mild cognitive impairment (MCI), comparing the results with those obtained in age-matched healthy controls (HC). 186 individuals were enrolled in the study: 67 AD, 58 MCI, and 61 HC. HSV-1 IgG titers and subclasses, neutralizing antibody (NAb) titers, and complement C3 concentration-critical component of antibody-mediated effector activity-were measured in sera by ELISA; IgG neutralizing activity was performed on HSV-1 infected Vero cells. Results showed that, whereas HSV-1-specific IgG(1), IgG(2), and IgG(4) titers as well as complement C3 serum concentration were comparable in all groups of individuals, IgG(3) were more frequently detected in MCI (89%) compared to AD (75%; p < 0.05) and HC (68%; p = 0.003), whereas the titer is similar among the three groups (AD: 0.66 +/- 0.21 OD; MCI: 0.68 +/- 0.24 OD; HC: 0.72 +/- 0.28 OD). Notably, HSV-1 specific neutralizing ability of AD sera was reduced even in the presence of high quantity of IgG(3). As IgG(3) plays a key role in counteracting the ability of HSV-1 to evade immune responses, these data reinforce the hypothesis of a pathogenetic role of HSV-1 in AD.