ArticleJournal of neuroinflammation2023
Septin-3 autoimmunity in patients with paraneoplastic cerebellar ataxia.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 20 citations in OpenAlex.
- Septin multimer autoantibodies in severe motor neuropathy mimicking lower motor neuron disease.Brain : a journal of neurology · 2026Article
- Copine-5-IgG-related autoimmune encephalitis: a novel paraneoplastic neurological syndrome with a strong melanoma association.Journal of neuroinflammation · 2026Article
- Seeing elephants and drinking water from a porcelain vase - A case of septin-7 antibody-associated encephalitis presenting as a severe disorganized psychosis.Translational psychiatry · 2026Article
- Mimics and Diagnostic Pitfalls of Anti-Adenylate Kinase 5 Limbic Encephalitis.CNS neuroscience & therapeutics · 2026Article
- Revealing Causal Protein Biomarkers and Potential Therapeutic Targets for Histologic-Specific Lung Cancer.Journal of cellular and molecular medicine · 2025Article
- Septins in the nervous system: from cytoskeletal dynamics to neurological disorders.Cell communication and signaling : CCS · 2025Review
- Anti-septin complex positive autoimmune encephalitis after severe falciparum malaria: a case report.Malaria journal · 2024Article
- Identification of DAGLA as an autoantibody target in cerebellar ataxia.Journal of neurology, neurosurgery, and psychiatry · 2024Article
- Detection of High-Risk Paraneoplastic Antibodies against TRIM9 and TRIM67 Proteins.Annals of neurology · 2023Article
- Case report: Anti septin-5-encephalitis as a treatable cause of cerebellar ataxia and psychiatric symptoms.Frontiers in neurology · 2023Article
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13 authors at 5 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundSeptins are cytoskeletal proteins with filament forming capabilities, which have multiple roles during cell division, cellular polarization, morphogenesis, and membrane trafficking. Autoantibodies against septin-5 are associated with non-paraneoplastic cerebellar ataxia, and autoantibodies against septin-7 with encephalopathy with prominent neuropsychiatric features. Here, we report on newly identified autoantibodies against septin-3 in patients with paraneoplastic cerebellar ataxia. We also propose a strategy for anti-septin autoantibody determination.
methodsSera from three patients producing similar immunofluorescence staining patterns on cerebellar and hippocampal sections were subjected to immunoprecipitation followed by mass spectrometry. The identified candidate antigens, all of which were septins, were expressed recombinantly in HEK293 cells either individually, as complexes, or combinations missing individual septins, for use in recombinant cell-based indirect immunofluorescence assays (RC-IIFA). Specificity for septin-3 was further confirmed by tissue IIFA neutralization experiments. Finally, tumor tissue sections were analyzed immunohistochemically for septin-3 expression.
resultsImmunoprecipitation with rat cerebellum lysate revealed septin-3, -5, -6, -7, and -11 as candidate target antigens. Sera of all three patients reacted with recombinant cells co-expressing septin-3/5/6/7/11, while none of 149 healthy control sera was similarly reactive. In RC-IIFAs the patient sera recognized only cells expressing septin-3, individually and in complexes. Incubation of patient sera with five different septin combinations, each missing one of the five septins, confirmed the autoantibodies' specificity for septin-3. The tissue IIFA reactivity of patient serum was abolished by pre-incubation with HEK293 cell lysates overexpressing the septin-3/5/6/7/11 complex or septin-3 alone, but not with HEK293 cell lysates overexpressing septin-5 as control. All three patients had cancers (2 × melanoma, 1 × small cell lung cancer), presented with progressive cerebellar syndromes, and responded poorly to immunotherapy. Expression of septin-3 was demonstrated in resected tumor tissue available from one patient.
conclusionsSeptin-3 is a novel autoantibody target in patients with paraneoplastic cerebellar syndromes. Based on our findings, RC-IIFA with HEK293 cells expressing the septin-3/5/6/7/11 complex may serve as a screening tool to investigate anti-septin autoantibodies in serological samples with a characteristic staining pattern on neuronal tissue sections. Autoantibodies against individual septins can then be confirmed by RC-IIFA expressing single septins.
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