Biomarkers of neural integrity and immunoglobulin genes influence neurodegeneration in Alzheimer's disease.

Autor: Pandey JP; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC, USA. Electronic address: pandeyj@musc.edu., Baglio F; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy., Mancuso R; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy., Guerini FR; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy., Cabinio M; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy., Isernia S; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy., Clerici M; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy., Agostini S; IRCCS Fondazione Don Carlo Gnocchi ONLUS, Milan, Italy.
Jazyk: angličtina
Zdroj: Journal of the neurological sciences [J Neurol Sci] 2024 Sep 15; Vol. 464, pp. 123167. Date of Electronic Publication: 2024 Aug 05.
DOI: 10.1016/j.jns.2024.123167
Abstrakt: Compelling evidence has been presented in favor of herpes simplex virus type 1 (HSV1) being one of the causative agents of Alzheimer's disease (AD). The success of HSV1 as a pathogen relates to its sophisticated strategies to evade host immunosurveillance. One strategy involves encoding a decoy Fcγ receptor (FcγR) that thwarts the Fcγ-mediated effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), a potent host immunosurveillance mechanism against virally infected cells. The decoy FcγR binds to antibodies of all IgG subclasses, except IgG3; therefore, IgG3 would be expected to play an important role in viral clearance by neutralization and ADCC, and thus contribute to protection from HSV1-spurred diseases. Previous studies have shown significant association between anti-HSV1 IgG3 antibodies and cortical thinning of the areas of the brain typically altered in AD and also targeted by HSV1. The aim of the present investigation was to determine whether GM (γ marker) 5 and GM 21 allotypes, hereditary allelic determinants expressed on IgG3, together with brain biomarkers of neural integrity, contributed to neurodegeneration-as measured by mini-mental state examination (MMSE) score-in patients with AD. Multiple regression analyses showed that the homozygous GM 5/5 genotype, preserved right hippocampus, and right insula thickness were associated with higher MMSE scores (p < 0.001), whereas the opposite pattern and GM 5/21 genotype were associated with worse clinical profiles. Influence of GM 5/21-expressing IgG3 antibodies on the ADCC of HSV1-infected neurons could, at least partially, explain these results.
Competing Interests: Declaration of competing interest The authors report no competing financial interest.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: