Abstract
Objective
To describe the clinical associations of SOX1 antibodies (SOX1-Abs), determine the accuracy of various detection techniques, and propose laboratory criteria to identify definite paraneoplastic neurological syndromes (PNS) associated with SOX1-Abs.
Methods
Single-center, retrospective study of patients referred to the French Reference Center between 2009 and 2019 for confirmation of SOX1-Ab positivity, without concurrent neural antibodies. Patients were classified according to the updated diagnostic PNS criteria; biological samples were systematically retested with three distinct techniques (line blot, cell-based assay, indirect immunofluorescence).
Results
Among 77 patients with isolated SOX1-Ab positivity, 23 (29.9%) fulfilled the criteria for definite PNS; all of them had lung cancer (mostly small-cell) and presented mainly with Lambert-Eaton myasthenic syndrome (10/23) and rapidly progressive cerebellar ataxia (6/23). SOX1-Ab positivity varied depending on the laboratory methods which were used, and a single technique was not sufficient to draw conclusions about the PNS diagnosis. The combination of an antigen-specific test (line blot and/or cell-based assay) and immunofluorescence showed the highest accuracy (81.5%, 95% CI 70.0–90.1) in identifying definite PNS. Moreover, when the PNS-Care score was recalculated assigning three points at the laboratory-level only to patients with positive “antigenic-specific test + immunofluorescence” and 0 points to the remaining cases, a higher certainty for definite and non-PNS was achieved (from 41/77, 53.2%, to 60/77, 77.9%; p < 0.001).
Conclusion
SOX1-Abs should be considered high-risk antibodies only when detected with a positive antigenic-specific test and immunofluorescence. Other laboratory results and clinical associations different from Lambert-Eaton myasthenic syndrome and rapidly progressive cerebellar ataxia should be carefully reassessed to rule out false positivity and alternative diagnoses.
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Any data not published within the article are available and will be shared by request from any qualified investigator.
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Acknowledgements
We thank NeuroBioTec Hospices Civils de Lyon BRC (France, AC-2013-1867, NFS96-900) for banking sera and CSF samples.
Funding
This work is supported by a public grant overseen by the Agence nationale de la recherche (ANR; French research agency) as part of the “Investissements d’Avenir” program (ANR-18-RHUS-0012). This study was performed within the framework of the LABEX CORTEX of the Université Claude Bernard Lyon 1, within the program “Investissements d'Avenir” (ANR-11-LABX-0042) operated by the ANR.
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Study concept and design: MV, JH, SMC. Acquisition of data: MV, ALP, AV, DG, VR, BJ, NF, JH, SMC. Analysis and interpretation of data: MV, ALP, AV, JH, SMC. Drafting of the manuscript: MV, JH, SMC. Critical revision of the manuscript for important intellectual content: MV, ALP, AV, DG, VR, BJ, NF, JH, SMC. All the authors approved the final version of the manuscript.
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Observational studies conducted in France using data obtained from a retrospective study without any additional therapeutic or monitoring procedure do not require informed consent. Patient records and information were anonymized prior to analysis. The Institutional Review Board of the University Claude Bernard Lyon 1 and Hospices Civils de Lyon approved the study.
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Vabanesi, M., Pinto, AL., Vogrig, A. et al. SOX1 antibody-related paraneoplastic neurological syndromes: clinical correlates and assessment of laboratory diagnostic techniques. J Neurol 270, 1691–1701 (2023). https://doi.org/10.1007/s00415-022-11523-y
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DOI: https://doi.org/10.1007/s00415-022-11523-y