[Pubmed] Autoantibody Profiles of Immune Checkpoint Inhibitor-Associated Myasthenia and Myositis

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Cancer Control. 2026 Jan-Dec;33:10732748261493412. doi: 10.1177/10732748261493412. Epub 2026 Sep 29.

ABSTRACT

IntroductionImmune 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.MethodsThis 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.ResultsAmong 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.ConclusionIn 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.

PMID:42810719 | DOI:10.1177/10732748261493412


Source: https://pubmed.ncbi.nlm.nih.gov/4281071 ... 5&v=2.20.1