Don Carlo Gnocchi Foundation IRCCS - ONLUS, Milan, Italy.
Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
J Alzheimers Dis. 2018;63(1):131-138. doi: 10.3233/JAD-170966.
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 IgG3. 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 IgG1, IgG2, and IgG4 titers as well as complement C3 serum concentration were comparable in all groups of individuals, IgG3 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 IgG3. As IgG3 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.
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）的发展中起作用。免疫球蛋白 G（IgG）中和 HSV-1 的活性，但该病毒可以通过表达受体来逃避 IgG 介导的免疫反应，该受体有效地结合除 IgG3 以外的所有 IgG 亚类的 Fc 部分。我们分析了诊断为 AD 或轻度认知障碍（MCI）的个体中针对 HSV-1 的 HSV-1 特异性 IgG 亚类和 IgG 介导的血清中和活性，并将结果与年龄匹配的健康对照（HC）进行比较。共有 186 人入组研究：67 例 AD、58 例 MCI 和 61 例 HC。通过 ELISA 测量血清中的 HSV-1 IgG 滴度和亚类、中和抗体（NAb）滴度和补体 C3 浓度 - 抗体介导的效应物活性的关键组成部分；在感染 HSV-1 的 Vero 细胞上进行 IgG 中和活性。结果表明，虽然所有组别的 HSV-1 特异性 IgG1、IgG2 和 IgG4 滴度以及补体 C3 血清浓度相似，但在 MCI 中更频繁地检测到 IgG3（89%）与 AD（75%；p <0.05）和 HC（68%；p =0.003），而三组之间的滴度相似（AD：0.66±0.21 OD；MCI：0.68±0.24 OD；HC：0.72±0.28 OD）。值得注意的是，即使存在大量 IgG3，AD 血清的 HSV-1 特异性中和能力也降低了。由于 IgG3 在抵抗 HSV-1 逃避免疫反应的能力方面起着关键作用，这些数据加强了 HSV-1 在 AD 中的致病作用的假说。
