Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity.

Abstract:

: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.

journal_name

Front Neurol

journal_title

Frontiers in neurology

authors

Zhu M,Ma Y,Zekeridou A,Lennon VA

doi

10.3389/fneur.2020.598894

subject

Has Abstract

pub_date

2020-12-10 00:00:00

pages

598894

issn

1664-2295

journal_volume

11

pub_type

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