Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing
Background and AimsReliable detection of antibodies against nodal targets is vital for the diagnosis of autoimmune nodopathies. The performance characteristics of recently developed in-house assays are unknown. We compared testing at four centres.MethodsEach submitted 29-40 serum samples to a coordi...
| Autores: | , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repositorio: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p21185 |
| Acceso en línea: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21185 |
| Access Level: | acceso abierto |
| Palabra clave: | autoantibodies CASPR1 contactin-1 immunoassay neurofascin |
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Inter-Laboratory Validation of Nodal/Paranodal Antibody TestingLleixà, CTitulaer, MRohrbacher, SMgbachi, VHalstead, SFehmi, JPascual-Goñi, EZhu, LAppeltshauser, LFranken, SPaunovic, MWaters, PWillison, HSommer, CQuerol, LHuizinga, RDoppler, KRinaldi, SautoantibodiesCASPR1contactin-1immunoassayneurofascinBackground and AimsReliable detection of antibodies against nodal targets is vital for the diagnosis of autoimmune nodopathies. The performance characteristics of recently developed in-house assays are unknown. We compared testing at four centres.MethodsEach submitted 29-40 serum samples to a coordinating centre from one of three groups: (1) autoimmune nodopathy patients, with positive nodal/paranodal antibodies; (2) seronegative patients with other inflammatory neuropathies, and (3) healthy individuals or those with other neurological diseases. The coordinating centre recoded all samples and returned 160 identical aliquots to each testing centre for blinded testing. Once data from all centres had been received by the coordinating centre, unblinded results were returned for analysis. Sensitivity was defined by the proportion of group 1 samples returned as positive. Accuracy was defined as 0.075(sensitivity) + 0.925(specificity).ResultsCentres performed various combinations of ELISA, cell-based (CBAs) and teased-nerve fibre assays. All labs produced highly accurate results (96%-100%) and concordance for the overall result across at least 3 or all 4 test centres was observed for 98% and 89% of the samples respectively. However, 10/30 individual assays (6/14 CBAs and 4/16 ELISAs) were less than 90% sensitive. Only 3 assays had more than 1 false positive result (2 ELISAs and 1 CBA). Combining different assay modalities to produce an overall result did not improve accuracy. Inter-laboratory consistency in the determination of antibody subclasses was poor.InterpretationAlthough most samples were correctly categorised in all 4 centres, the use of a specific test modality or multiple tests did not guarantee accuracy. Early and repeated interlaboratory testing with sharing of samples is important to understand test performance and reproducibility, identify areas for improvement and maintain consistency. To aid this, we provide detailed methods for the best performing tests. Further standardisation of antibody subclass determination is required.WILEY2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21185JOURNAL OF THE PERIPHERAL NERVOUS SYSTEMISSN: 10859489ISSNe: 15298027reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pauinstname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)Inglésinfo:eu-repo/semantics/openAccessoai:iibsantpau.fundanetsuite.com:p211852026-06-14T12:41:47Z |
| dc.title.none.fl_str_mv |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing |
| title |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing |
| spellingShingle |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing Lleixà, C autoantibodies CASPR1 contactin-1 immunoassay neurofascin |
| title_short |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing |
| title_full |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing |
| title_fullStr |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing |
| title_full_unstemmed |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing |
| title_sort |
Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing |
| dc.creator.none.fl_str_mv |
Lleixà, C Titulaer, M Rohrbacher, S Mgbachi, V Halstead, S Fehmi, J Pascual-Goñi, E Zhu, L Appeltshauser, L Franken, S Paunovic, M Waters, P Willison, H Sommer, C Querol, L Huizinga, R Doppler, K Rinaldi, S |
| author |
Lleixà, C |
| author_facet |
Lleixà, C Titulaer, M Rohrbacher, S Mgbachi, V Halstead, S Fehmi, J Pascual-Goñi, E Zhu, L Appeltshauser, L Franken, S Paunovic, M Waters, P Willison, H Sommer, C Querol, L Huizinga, R Doppler, K Rinaldi, S |
| author_role |
author |
| author2 |
Titulaer, M Rohrbacher, S Mgbachi, V Halstead, S Fehmi, J Pascual-Goñi, E Zhu, L Appeltshauser, L Franken, S Paunovic, M Waters, P Willison, H Sommer, C Querol, L Huizinga, R Doppler, K Rinaldi, S |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
autoantibodies CASPR1 contactin-1 immunoassay neurofascin |
| topic |
autoantibodies CASPR1 contactin-1 immunoassay neurofascin |
| description |
Background and AimsReliable detection of antibodies against nodal targets is vital for the diagnosis of autoimmune nodopathies. The performance characteristics of recently developed in-house assays are unknown. We compared testing at four centres.MethodsEach submitted 29-40 serum samples to a coordinating centre from one of three groups: (1) autoimmune nodopathy patients, with positive nodal/paranodal antibodies; (2) seronegative patients with other inflammatory neuropathies, and (3) healthy individuals or those with other neurological diseases. The coordinating centre recoded all samples and returned 160 identical aliquots to each testing centre for blinded testing. Once data from all centres had been received by the coordinating centre, unblinded results were returned for analysis. Sensitivity was defined by the proportion of group 1 samples returned as positive. Accuracy was defined as 0.075(sensitivity) + 0.925(specificity).ResultsCentres performed various combinations of ELISA, cell-based (CBAs) and teased-nerve fibre assays. All labs produced highly accurate results (96%-100%) and concordance for the overall result across at least 3 or all 4 test centres was observed for 98% and 89% of the samples respectively. However, 10/30 individual assays (6/14 CBAs and 4/16 ELISAs) were less than 90% sensitive. Only 3 assays had more than 1 false positive result (2 ELISAs and 1 CBA). Combining different assay modalities to produce an overall result did not improve accuracy. Inter-laboratory consistency in the determination of antibody subclasses was poor.InterpretationAlthough most samples were correctly categorised in all 4 centres, the use of a specific test modality or multiple tests did not guarantee accuracy. Early and repeated interlaboratory testing with sharing of samples is important to understand test performance and reproducibility, identify areas for improvement and maintain consistency. To aid this, we provide detailed methods for the best performing tests. Further standardisation of antibody subclass determination is required. |
| publishDate |
2025 |
| dc.date.none.fl_str_mv |
2025 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21185 |
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https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=21185 |
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Inglés |
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Inglés |
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info:eu-repo/semantics/openAccess |
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openAccess |
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WILEY |
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WILEY |
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JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM ISSN: 10859489 ISSNe: 15298027 reponame:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
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