Debate on the pathogenesis of paraneoplastic cerebellar degeneration with anti‐Yo antibody: T‐cell mediated or antibody mediated?

Tanaka, Keiko

doi:10.1111/cen3.12234

Cited by 1 publication

(2 citation statements)

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“…Paraneoplastic neurological syndrome with antibodies specific for intracellular antigens is widely considered to be a cytotoxic T cellmediated disease caused by anticancer immunity [40]. During this process, co-activation of the humoural immune mechanism is induced, and autoantibodies against onconeural antigens are produced.…”

Section: Anti-neural Antigens Resultsmentioning

confidence: 99%

“…During this process, co-activation of the humoural immune mechanism is induced, and autoantibodies against onconeural antigens are produced. These neoplastic proteins are usually located in the cytoplasm or nucleus of neurons and are not targets of antibody-mediated neuronal damage [40]. Ganglioside, such as GQ1b, are well-known extracellular antigens; thus, the production of both anti-Hu antibodies and anti-GQ1b antibodies is caused by a state in which the immunological mechanism is widely activated by the cancer itself.…”

Section: Anti-neural Antigens Resultsmentioning

confidence: 99%

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Paraneoplastic cerebellar degeneration and limbic/brainstem encephalopathy associated with small cell lung cancer with serum positivity for anti-Hu and multiple anti-ganglioside (GM2, GQ1b, GaLNAc-GD1a, GT1a) antibodies: A case report

Nokura¹,

Kako²,

Azuma³

et al. 2020

Neuro Neurosurg

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Background: Anti-Hu antibodies are known to appear in paraneoplastic neurologic syndrome associated with small cell lung cancer. Miller Fisher syndrome, Guillain-Barré syndrome, and Bickerstaff brainstem encephalitis lie on the same disease spectrum, and cancer is reported to be one of the prodromal events of this disorder; the anti-GQ1b antibody is pathognomonic for diagnosing this spectrum. On the other hand, ganglioside expression in cancer cells is related to signal transmission, such as that involved in cancer growth and metastasis; furthermore, anti-ganglioside antibodies might be produced in the context of cancer. Case presentation:A 65-year-old man without a specific history other than smoking and alcohol consumption developed difficulty speaking and walking with subacute onset. Eye movements were normal, and tendon reflexes were only partially reduced; remarkable truncal ataxia and dysarthria were observed. The patient was hospitalized for suspected Miller Fisher syndrome because he tested positive for serum GQ1b antibodies. Intravenous immunoglobulin was administered without any effect. Subsequent PET-CT examination showed positive lesions in the hilar and supraclavicular lymph nodes; a biopsy revealed a diagnosis of small cell lung cancer, and chemotherapy was initiated. Subsequently, delusions and abnormal behaviour appeared. A brain MRI showed a high signal intensity in the hippocampus, and the patient was found to be positive for serum anti-Hu antibodies. Central hypoventilation and dysphagia were also observed; we finally diagnosed him as having paraneoplastic cerebellar degeneration with limbic/brainstem encephalitis. The patient died two months later from pneumonia. It is unclear whether the antiganglioside antibody positivity in this patient followed any infection or was caused by small cell lung cancer. Whether the pathogenetic mechanisms mediated by anti-GQ1b antibodies were actually superimposed on cerebellar degeneration is unknown. These antibodies might be produced under a hyper-immune state induced by cancer.Conclusions: This is the first reported case of cerebellar degeneration and limbic/brainstem encephalopathy accompanied by small cell lung cancer; in this case, the patient was positive for anti-Hu and multiple anti-ganglioside antibodies. The implications of anti-ganglioside antibody production in cancer should be elucidated in the future, and a screening of ganglioside antibodies should be recommended as a potential future study.

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Section: Anti-neural Antigens Resultsmentioning

confidence: 99%

Section: Anti-neural Antigens Resultsmentioning

confidence: 99%