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Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis

Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the fi...

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Autores principales: Greenlee, John E., Carlson, Noel G., Abbatemarco, Justin R., Herdlevær, Ida, Clardy, Stacey L., Vedeler, Christian A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801577/
https://www.ncbi.nlm.nih.gov/pubmed/35111121
http://dx.doi.org/10.3389/fneur.2021.744653
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author Greenlee, John E.
Carlson, Noel G.
Abbatemarco, Justin R.
Herdlevær, Ida
Clardy, Stacey L.
Vedeler, Christian A.
author_facet Greenlee, John E.
Carlson, Noel G.
Abbatemarco, Justin R.
Herdlevær, Ida
Clardy, Stacey L.
Vedeler, Christian A.
author_sort Greenlee, John E.
collection PubMed
description Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients.
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spelling pubmed-88015772022-02-01 Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis Greenlee, John E. Carlson, Noel G. Abbatemarco, Justin R. Herdlevær, Ida Clardy, Stacey L. Vedeler, Christian A. Front Neurol Neurology Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients. Frontiers Media S.A. 2022-01-17 /pmc/articles/PMC8801577/ /pubmed/35111121 http://dx.doi.org/10.3389/fneur.2021.744653 Text en Copyright © 2022 Greenlee, Carlson, Abbatemarco, Herdlevær, Clardy and Vedeler. https://creativecommons.org/licenses/by/4.0/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.
spellingShingle Neurology
Greenlee, John E.
Carlson, Noel G.
Abbatemarco, Justin R.
Herdlevær, Ida
Clardy, Stacey L.
Vedeler, Christian A.
Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
title Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
title_full Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
title_fullStr Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
title_full_unstemmed Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
title_short Paraneoplastic and Other Autoimmune Encephalitides: Antineuronal Antibodies, T Lymphocytes, and Questions of Pathogenesis
title_sort paraneoplastic and other autoimmune encephalitides: antineuronal antibodies, t lymphocytes, and questions of pathogenesis
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8801577/
https://www.ncbi.nlm.nih.gov/pubmed/35111121
http://dx.doi.org/10.3389/fneur.2021.744653
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