TMEM132A autoimmunity in patients with suspected autoimmune cerebellar ataxia.

Authors

Akio Kimura, Akira Takekoshi, Yuri Miyazaki, Kentaro Oh-Hashi, Sachiko Kamada, Yukie Taguchi, Masashiro Sugawara, Tsubasa Watanabe, Yuji Ueno, Hiroaki Yaguchi, Ichiro Yabe, Yuko Fukata, Masaki Fukata, Takayoshi Shimohata

Published in

Journal of neuroimmunology. Volume 413. Pages 578867. Jan 14, 2026. Epub Jan 14, 2026.

Abstract

Autoimmune cerebellar ataxia (ACA) refers to immune-mediated cerebellar ataxia. The autoantibodies involved in ACA can be detected in patients and are important biomarkers. In this study, we aimed to identify a novel autoantibody in patients with ACA. We screened for autoantibodies in serum samples from patients with cerebellar ataxia using immunohistochemical and immunocytochemical assays. Immunoprecipitation and mass spectrometry were used to identify the target antigens of the detected autoantibodies. We found that IgG reacted with transmembrane protein family 132 A (TMEM132A), which is enriched in the central nervous system (CNS), in serum samples of patients with cerebellar ataxia. A cell-based binding assay (CBA) was used to identify TMEM132A-IgG in serum samples obtained from 436 patients with cerebellar ataxia requiring differential diagnosis for ACA, 62 patients with autoimmune encephalitis, 27 patients with multiple system atrophy with predominant cerebellar ataxia, 24 patients with multiple sclerosis, 17 patients with neuromyelitis optica spectrum disorders, 17 patients with Parkinson's disease, 7 patients with anti-myelin oligodendrocyte glycoprotein antibody-associated disease, and 14 healthy subjects. We detected TMEM132A-IgG in serum samples from two patients with cerebellar ataxia, including the patient whose study first led to the identification of this autoantibody. None of the other participants had these autoantibodies. The two autoantibody-positive patients showed progressive predominant cerebellar ataxia with pyramidal tract signs and albuminocytologic dissociation. Brain MRI findings indicated cerebellar atrophy in one patient and bilateral inferior olivary nuclei hyperintensity changes and pseudohypertrophy in the other patient. TMEM132 A-IgG may be a novel autoantibody associated with autoimmune CNS diseases, including ACA.

PMID:
41564469
Bibliographic data and abstract were imported from PubMed on 22 Jan 2026.

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