AUTHOR=Zhu Mingqin , Ma Yuetao , Zekeridou Anastasia , Lennon Vanda A. 

TITLE=Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity

JOURNAL=Frontiers in Neurology

VOLUME=Volume 11 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.598894

DOI=10.3389/fneur.2020.598894

ISSN=1664-2295

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-alpha. We hypothesize that a pre-existing tumor-initiated autoimmune response (evidenced by autoantibody profiles) 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 CD8+ T cell killing, thus precipitating the patient’s neurological autoimmunity.