TY - JOUR
T1 - Case Report
T2 - Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity
AU - Zhu, Mingqin
AU - Ma, Yuetao
AU - Zekeridou, Anastasia
AU - Lennon, Vanda A.
N1 - Funding Information:
Study funded by the Mayo Clinic Foundation.
Publisher Copyright:
© Copyright © 2020 Zhu, Ma, Zekeridou and Lennon.
PY - 2020/12/10
Y1 - 2020/12/10
N2 - 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.
AB - 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.
KW - PAMPS
KW - cancer immunotherapy
KW - neural autoantibodies
KW - onconeural peptides
KW - paraneoplastic autoimmune neurological disorders
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U2 - 10.3389/fneur.2020.598894
DO - 10.3389/fneur.2020.598894
M3 - Article
AN - SCOPUS:85098178135
SN - 1664-2295
VL - 11
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 598894
ER -