In vivo Mechanisms of Antibody-Mediated Neurological Disorders:Animal Models and Potential Implications

Abstract

Over the last two decades, the discovery of antibodies directed against neuronal surface antigens (NSA-Abs) in patients with different forms of encephalitis has provided a basis for immunotherapies in previously undefined disorders. Nevertheless, despite the circumstantial clinical evidence of the pathogenic role of these antibodies in classical autoimmune encephalitis, specific criteria need to be applied in order to establish the autoimmune nature of a disease. A growing number of studies have begun to provide proof of the pathogenicity of NSA-Abs and insights into their pathogenic mechanisms through passive transfer or, more rarely, through active immunization animal models. Moreover, the increasing evidence that NSA-Abs in the maternal circulation can reach the fetal brain parenchyma during gestation, causing long-term effects, has led to models of antibody-induced neurodevelopmental disorders. This review summarizes different methodological approaches and the results of the animal models of N-methyl-d-aspartate receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein 2 (CASPR2), and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) antibody-mediated disorders and discuss the results and the limitations. We also summarize recent experiments that demonstrate that maternal antibodies to NMDAR and CASPR2 can alter development in the offspring with potential lifelong susceptibility to neurological or psychiatric disorders.

Publication DOI: https://doi.org/10.3389/fneur.2019.01394
Divisions: Life & Health Sciences > Pharmacy
Additional Information: © 2020 Giannoccaro, Wright and Vincent. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Uncontrolled Keywords: active immunization,animal models,maternal transfer,neuronal surface antibodies,passive transfer,Neurology,Clinical Neurology
Full Text Link:
Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
https://www.fro ... 2019.01394/full (Publisher URL)
PURE Output Type: Review article
Published Date: 2020-02-05
Accepted Date: 2019-12-19
Authors: Giannoccaro, Maria Pia
Wright, Sukhvir K. ( 0000-0002-5464-3779)
Vincent, Angela

Download

[img]

Version: Published Version

License: Creative Commons Attribution

| Preview

Export / Share Citation


Statistics

Additional statistics for this record