ArticleAnnals of clinical and translational neurology2026
Insights Into the Antigenic Repertoire of Unclassified Synaptic Antibodies.
Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Gephyrin Neurological Autoimmunity.Annals of neurology · 2026Article
- Novel methods for neural IgG characterization and validation in autoimmune neurologic disorders.Journal of immunological methods · 2026Review
- Testing for neural antibodies in autoimmune encephalitis: who, what, where, when, why, and how.Therapeutic advances in neurological disorders · 2026Review
- A unified spectrum model for the anti-GQ1b antibody syndromes: from pathophysiology to a new diagnostic framework.Frontiers in neurologyReview
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23 authors.
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Abstract
objectiveWe sought to characterize the sixth most common finding in our neuroimmunological laboratory practice (tissue assay-observed unclassified neural antibodies [UNAs]), combining protein microarray and phage immunoprecipitation sequencing (PhIP-Seq).
methodsPatient specimens (258; 133 serums; 125 CSF) meeting UNA criteria were profiled; October 2022-September 2023. Top-ranking candidate antigens were validated in silico, by dual-staining confocal microscopy, and ≥ 1 protein-specific assay. Clinical data were reviewed.
resultsAmong 21 patients, 11 autoantibodies were characterized (serum, 19; CSF, all 9 available). Autoantigens were CACNA1I, 1; CAMK2B, 2; CLIP2, 1; FMN2, 2; MAP1A, 2; MAP2, 5; NECAB1, 1; SNAP91, 3; SRCIN1, 1; SYNJ1, 1; SYT3, 2. Analytical validation was by confocal TIIFA (all), western blot (10/10 available), and cell-based assay (5/5 performed). Clinical accompaniments were: encephalitis, 6; brainstem encephalitis, 2; encephalomyelitis, 2; cerebellar ataxia, 2; longitudinally extensive transverse myelitis (LETM), 2; sensory neuronopathy, 1; peripheral neuropathy, 4, and movement disorders, 2. Inflammatory MRI abnormalities were identified in 5/16 patients (31%) with CNS disorders: T2 signal change (2), LETM (2), leptomeningeal enhancement (1). Seven of 8 (88%) had inflammatory CSF (pleocytosis, 5 [median 25.5 cells, range 7-294]; elevated IgG index/synthesis rate, 4; CSF-exclusive oligoclonal bands, 4). Six had paraneoplastic causation (lung cancer, 2; other, 4); 3 were postinfectious (1 each of COVID-19, HSV-1, and post-Group A streptococcal infection). Of 9 immunotherapy-treated patients, 5 improved.
interpretationUNAs are partly accounted for by a repertoire of diverse mostly intracellular synaptic antigens. Their characterization is expedited by protein arrays and PhIPSeq. Further individual studies are needed to assess them as disease biomarkers.
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