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Neurological disorders associated with immune checkpoint inhibitors: an association with autoantibodies

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Abstract

Among diverse neurological immune-related adverse events (irAEs), autoimmune encephalitis, aseptic meningitis, Guillain-Barré syndrome (GBS), myasthenia gravis (MG), and myositis are particularly important. The clinical presentation may be different from that of patients with conditions unrelated to immune checkpoint inhibitors (ICIs). Many of the autoantibodies detected in patients’ sera are committed to the pathogenesis, while the clinical significance of such autoantibodies in cases of neurological irAEs is different from the significance in cases of typical neuronal disorders. A broad range of clinical symptoms complicates the diagnosis of autoimmune encephalitis. The clinical features of aseptic meningitis induced by classical drugs are different from those of aseptic meningitis induced by ICIs. Although autoantibodies against synaptic receptors or neuronal cell surface proteins are not detected, anti-Ma2 antibodies, which are onconeural antibodies against intracellular proteins, are detected in patients with autoimmune encephalitis associated with ICIs. GBS induced by ICIs sometimes shows gradual progression and a relapse of symptoms, suggesting chronic inflammatory demyelinating polyneuropathy. Bulbar symptoms and myasthenic crisis are frequently observed in ICI-induced MG. Anti-acetylcholine receptor antibodies are found in only half of patients with MG occurring as an irAE. ICI-induced myositis is accompanied by ocular muscle symptoms, such as ptosis and diplopia, which can suggest MG. Patients receiving ICI treatment present clinical features and laboratory findings that represent a mixture of MG and myositis. Anti-striational antibodies may act as biomarkers in cases in which MG and myositis overlap. A correct understanding of neurological adverse events is required to achieve the best management of patients.

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Acknowledgements

This work was supported by JSPS KAKENHI Grant No. JP20H03592.

Funding

This work was funded by JSPS KAKENHI Grant Number JP20H03592.

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Authors and Affiliations

  1. Department of Neurology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan

    Morinobu Seki & Shigeaki Suzuki

  2. Division of Cancer Immunotherapy Development, Center for Advanced Medical Development, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan

    Shigehisa Kitano

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  1. Morinobu Seki
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  2. Shigehisa Kitano
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Contributions

Conception and design were contributed by all authors. Collection and assembly of data were contributed by all authors. Data analysis and interpretation were contributed by all authors. Manuscript writing was contributed by Shigeaki Suzuki and Morinobu Seki. Final approval of manuscript was contributed by all authors. All authors were accountable for all aspects of the work.

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Correspondence to Shigeaki Suzuki.

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Seki, M., Kitano, S. & Suzuki, S. Neurological disorders associated with immune checkpoint inhibitors: an association with autoantibodies. Cancer Immunol Immunother 71, 769–775 (2022). https://doi.org/10.1007/s00262-021-03053-9

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