ORIGINAL RESEARCH article
Front. Neurol.
Sec. Multiple Sclerosis and Neuroimmunology
B-cell Immune Repertoire analysis of autoimmune neurological syndrome with anti-GAD65 antibodies
1. CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
2. Department of Neurology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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Abstract
Autoimmune neurological syndromes (AINS) with anti-GAD65 antibodies include a series of autoimmune neurological diseases, such as limbic encephalitis (LE), stiff-person syndrome (SPS), and cerebellar ataxia (CA), among others. Despite the universal presence of anti-GAD65 antibodies in these syndromes, the clinical phenotypes of patients are diverse. Exploring the overall B-cell receptor (BCR) profile of patients with anti-GAD65 AINS may provide clues to the molecular pathological mechanisms underlying phenotypic diversity. In the present study, we performed a comprehensive analysis of the B-cell repertoire in patients with anti-GAD65 AINS, including patients with anti-GAD65 AINS (n = 9) and healthy controls (HC) (n=11). The results revealed significant differences in BCR clonal diversity, frequency of hypermutation, and CDR3 amino acid characteristics between the different subtypes of anti-GAD65 AINS patients. The heterogeneity in the characteristics of the BCR repertoire among anti-GAD65 AINS patients across each clinical subtype provides some explanation for the possible causes of the clinical subtypes to be analyzed and inferred. Meanwhile, the VDJ features and clonotypes with a high degree of correlation to anti-GAD65 AINS that we have uncovered provide potential molecular markers for more precise diagnosis of anti-GAD65 AINS.
Summary
Keywords
Glutamic acid decarboxylase-65 antibodies, Limbic Encephalitis, Cerebellar Ataxia, stiff person syndrome, immune repertoire
Received
18 July 2025
Accepted
29 December 2025
Copyright
© 2025 Dong, Fan, Ren, Sun, Guan and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Hongzhi Guan; Jing Wang
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