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Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity

Paraneoplastic autoimmune neurological disorders reflect tumor-initiated immune responses against onconeural antigens. Symptoms and signs can affect the central and/or peripheral nervous systems, neuromuscular junction or muscle, and typically evolve subacutely before an underlying neoplasm is disco...

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Autores principales: Zhu, Mingqin, Ma, Yuetao, Zekeridou, Anastasia, Lennon, Vanda A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759151/
https://www.ncbi.nlm.nih.gov/pubmed/33362700
http://dx.doi.org/10.3389/fneur.2020.598894
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author Zhu, Mingqin
Ma, Yuetao
Zekeridou, Anastasia
Lennon, Vanda A.
author_facet Zhu, Mingqin
Ma, Yuetao
Zekeridou, Anastasia
Lennon, Vanda A.
author_sort Zhu, Mingqin
collection PubMed
description Paraneoplastic autoimmune neurological disorders reflect tumor-initiated immune responses against onconeural antigens. Symptoms and signs can affect the central and/or peripheral nervous systems, neuromuscular junction or muscle, and typically evolve subacutely before an underlying neoplasm is discovered. We describe four patients whose neurological symptoms were precipitated by potent innate immune system challenges: bladder instillation of BCG, tick bite and an “alternative cancer therapy” with bacterial extracts and TNF-α. We hypothesize that a tumor-initiated autoimmune response (evidenced by autoantibody profiles), pre-dating the immune system challenge, was unmasked or amplified in these patients by cytokines released systemically from innate immune cells activated by microbial pathogen-associated molecular patterns (PAMPs). The resultant upregulation of cognate onconeural peptides as MHC1 protein complexes on neural cell surfaces would render those cells susceptible to killing by CD8+ T cells, thus precipitating the patient's neurological symptoms.
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spelling pubmed-77591512020-12-25 Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity Zhu, Mingqin Ma, Yuetao Zekeridou, Anastasia Lennon, Vanda A. Front Neurol Neurology Paraneoplastic autoimmune neurological disorders reflect tumor-initiated immune responses against onconeural antigens. Symptoms and signs can affect the central and/or peripheral nervous systems, neuromuscular junction or muscle, and typically evolve subacutely before an underlying neoplasm is discovered. We describe four patients whose neurological symptoms were precipitated by potent innate immune system challenges: bladder instillation of BCG, tick bite and an “alternative cancer therapy” with bacterial extracts and TNF-α. We hypothesize that a tumor-initiated autoimmune response (evidenced by autoantibody profiles), pre-dating the immune system challenge, was unmasked or amplified in these patients by cytokines released systemically from innate immune cells activated by microbial pathogen-associated molecular patterns (PAMPs). The resultant upregulation of cognate onconeural peptides as MHC1 protein complexes on neural cell surfaces would render those cells susceptible to killing by CD8+ T cells, thus precipitating the patient's neurological symptoms. Frontiers Media S.A. 2020-12-10 /pmc/articles/PMC7759151/ /pubmed/33362700 http://dx.doi.org/10.3389/fneur.2020.598894 Text en Copyright © 2020 Zhu, Ma, Zekeridou and Lennon. http://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
Zhu, Mingqin
Ma, Yuetao
Zekeridou, Anastasia
Lennon, Vanda A.
Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
title Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
title_full Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
title_fullStr Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
title_full_unstemmed Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
title_short Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
title_sort case report: innate immune system challenge unleashes paraneoplastic neurological autoimmunity
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7759151/
https://www.ncbi.nlm.nih.gov/pubmed/33362700
http://dx.doi.org/10.3389/fneur.2020.598894
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