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Open AccessArticle

HSV-1-Specific IgG3 Titers Correlate with Brain Cortical Thinning in Individuals with Mild Cognitive Impairment and Alzheimer’s Disease

1
IRCCS Fondazione Don Carlo Gnocchi, 20148 Milano, Italy
2
Department of Pathophysiology and Transplantation, University of Milano, 20148 Milano, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Vaccines 2020, 8(2), 255; https://doi.org/10.3390/vaccines8020255
Received: 29 April 2020 / Revised: 25 May 2020 / Accepted: 26 May 2020 / Published: 29 May 2020
(This article belongs to the Special Issue Vaccine Development for Herpes Simplex Viruses)
Repeated reactivations of latent herpes simplex virus type-1 (HSV-1) in the central nervous system (CNS) may contribute to neurodegeneration in Alzheimer’s disease (AD) patients. Immune response is a key element for the control of viral reactivation. HSV-1 uses a number of strategies to evade immune recognition, Immunoglobulin G 3 (IgG3) alone counteracts humoral immunoevasion, as it is the only IgG subclass that is not blocked by the HSV-1 Fc receptor, a protein that protects virion and infected cells from antibody-mediated effector mechanisms. We examined HSV-1-specific IgG3 titers in serum of AD (n = 70) and mild cognitive impairment (MCI) (n = 61) subjects comparing the results to those of 67 age- and sex-matched healthy controls (HC); associations between MRI-determined brain cortical health and HSV-1-specific IgG3 were analyzed in a subgroup of AD and MCI subjects. HSV-1-specific IgG3 were more frequently detected in MCI compared to AD and HC subjects. Significant inverse correlations were found between IgG3 titers and brain cortical thickness in areas typically involved in dementia and HSV-1 encephalitis in AD patients; interestingly, this negative correlation was much less important in MCI subjects. All together these results suggest that in AD an inefficient IgG3 humoral immune response, failing to block viral replication, contributes to progressive neurodegeneration. View Full-Text
Keywords: Alzheimer’s disease; HSV-1; HSV-1-IgG subclasses; IgG3; mild cognitive impairment; magnetic resonance imaging (MRI) Alzheimer’s disease; HSV-1; HSV-1-IgG subclasses; IgG3; mild cognitive impairment; magnetic resonance imaging (MRI)
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Mancuso, R.; Cabinio, M.; Agostini, S.; Baglio, F.; Clerici, M. HSV-1-Specific IgG3 Titers Correlate with Brain Cortical Thinning in Individuals with Mild Cognitive Impairment and Alzheimer’s Disease. Vaccines 2020, 8, 255.

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