Autoantibody Profiles of Immune Checkpoint Inhibitor-Associated Myasthenia and Myositis
7 affiliations
- 1Department of Neurology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
- 2Autoimmune Laboratory, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
- 3Department of Neurology, Keio University School of Medicine, Tokyo, Japan
- 4Department of Laboratory Medicine and Pathology, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan
- 5Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
- 6Department of Neurology, The Jikei University School of Medicine, Kashiwa Hospital, Chiba, Japan
- 7Research Promotion Center, Tokyo Metropolitan Hospital Organization, Tokyo, Japan
Abstract
Introduction: Immune checkpoint inhibitor (ICI)-associated myasthenia and myositis are rare, potentially life-threatening neuromuscular immune-related adverse events, but their serological spectrum remains incompletely characterized. This study aimed to elucidate their autoantibody profiles and explore associations with severe clinical features.
Methods: This retrospective, multicenter, serum-repository-based observational cohort study included 50 patients with ICI-associated myasthenia and myositis referred from institutions throughout Japan. Clinical data and serum samples were analyzed using conventional autoantibody assays, cytometric cell-based assays, RNA immunoprecipitation, and immunohistochemistry. Antibody–outcome associations were evaluated exploratorily using Firth logistic regression.
Results: Among 50 patients, the median age was 71.5 years, and 35 (70%) were male. Two patients had preexisting thymoma-associated myasthenia. Underlying malignancies were diverse and included thoracic, gastrointestinal, urological, and other cancers. All but one patient received programmed cell death protein-1 inhibitors. The median interval from the first ICI administration to symptom onset was 31.5 days, although 7 patients showed delayed onset beyond 62 days. Severe toxicity, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 4 or 5, occurred in 15 patients, respiratory insufficiency in 12, and myocarditis in 9. Anti-acetylcholine receptor (AChR) antibodies were detected in 9 patients (18%) and showed exploratory associations with severe toxicity and respiratory insufficiency, although anti-muscle-specific kinase antibodies were not detected. Among striational antibodies, anti-titin and anti-Kv1.4 antibodies were detected in 21 and 22 patients, respectively. Anti-Kv1.4 antibodies showed an exploratory association with myocarditis. All 7 weak myositis-specific immunodot reactivities involved RNA-associated targets and lacked corresponding RNA immunoprecipitates. Reactivity on commercial paraneoplastic neurological syndrome (PNS) immunodot assays, accompanied by supportive neuronal tissue reactivity, was observed in 5 patients without classical PNS manifestations.
Conclusion: In this retrospective referral cohort, anti-AChR and anti-Kv1.4 reactivities showed exploratory associations with selected severe clinical features. These findings require prospective external validation.
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BibTeX
@article{kawazoe2026autoantibody,
title = {{Autoantibody Profiles of Immune Checkpoint Inhibitor-Associated Myasthenia and Myositis}},
author = {Tomoya Kawazoe and Toshiki Tezuka and Keisuke Ishizawa and Yoshiyuki Matsuki and Masatoshi Kawai and Akihito Hao and Takanobu Iri and Hiroshi Yaguchi and Funato Sato and Morinobu Seki and Kazushi Takahashi and Shigeaki Suzuki},
journal = {Cancer Control: Journal of the Moffitt Cancer Center},
year = {2026},
month = sep,
doi = {10.1177/10732748261493412},
url = {https://doi.org/10.1177/10732748261493412},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Autoantibody Profiles of Immune Checkpoint Inhibitor-Associated Myasthenia and Myositis
AU - Tomoya Kawazoe
AU - Toshiki Tezuka
AU - Keisuke Ishizawa
AU - Yoshiyuki Matsuki
AU - Masatoshi Kawai
AU - Akihito Hao
AU - Takanobu Iri
AU - Hiroshi Yaguchi
AU - Funato Sato
AU - Morinobu Seki
AU - Kazushi Takahashi
AU - Shigeaki Suzuki
PY - 2026
DA - 2026/09/29
JO - Cancer Control: Journal of the Moffitt Cancer Center
DO - 10.1177/10732748261493412
UR - https://doi.org/10.1177/10732748261493412
AB - Introduction: Immune checkpoint inhibitor (ICI)-associated myasthenia and myositis are rare, potentially life-threatening neuromuscular immune-related adverse events, but their serological spectrum remains incompletely characterized. This study aimed to elucidate their autoantibody profiles and explore associations with severe clinical features. Methods: This retrospective, multicenter, serum-repository-based observational cohort study included 50 patients with ICI-associated myasthenia and myositis referred from institutions throughout Japan. Clinical data and serum samples were analyzed using conventional autoantibody assays, cytometric cell-based assays, RNA immunoprecipitation, and immunohistochemistry. Antibody–outcome associations were evaluated exploratorily using Firth logistic regression. Results: Among 50 patients, the median age was 71.5 years, and 35 (70%) were male. Two patients had preexisting thymoma-associated myasthenia. Underlying malignancies were diverse and included thoracic, gastrointestinal, urological, and other cancers. All but one patient received programmed cell death protein-1 inhibitors. The median interval from the first ICI administration to symptom onset was 31.5 days, although 7 patients showed delayed onset beyond 62 days. Severe toxicity, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade 4 or 5, occurred in 15 patients, respiratory insufficiency in 12, and myocarditis in 9. Anti-acetylcholine receptor (AChR) antibodies were detected in 9 patients (18%) and showed exploratory associations with severe toxicity and respiratory insufficiency, although anti-muscle-specific kinase antibodies were not detected. Among striational antibodies, anti-titin and anti-Kv1.4 antibodies were detected in 21 and 22 patients, respectively. Anti-Kv1.4 antibodies showed an exploratory association with myocarditis. All 7 weak myositis-specific immunodot reactivities involved RNA-associated targets and lacked corresponding RNA immunoprecipitates. Reactivity on commercial paraneoplastic neurological syndrome (PNS) immunodot assays, accompanied by supportive neuronal tissue reactivity, was observed in 5 patients without classical PNS manifestations. Conclusion: In this retrospective referral cohort, anti-AChR and anti-Kv1.4 reactivities showed exploratory associations with selected severe clinical features. These findings require prospective external validation.
SN - 1073-2748
SN - 1526-2359
ER -