Determination of CSF GFAP, CCN5, and vWF Levels Enhances the Diagnostic Accuracy of Clinically Defined MS From Non-MS Patients With CSF Oligoclonal Bands.
Authors
Probert, Fay
Yeo, Tianrong
Zhou, Yifan
Sealey, Megan
Arora, Siddharth
Palace, Jacqueline
Claridge, Timothy DW
Hillenbrand, Rainer
Oechtering, Johanna
Kuhle, Jens
Leppert, David
Anthony, Daniel C
Publication Date
2021Journal Title
Front Immunol
ISSN
1664-3224
Publisher
Frontiers Media SA
Volume
12
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Probert, F., Yeo, T., Zhou, Y., Sealey, M., Arora, S., Palace, J., Claridge, T. D., et al. (2021). Determination of CSF GFAP, CCN5, and vWF Levels Enhances the Diagnostic Accuracy of Clinically Defined MS From Non-MS Patients With CSF Oligoclonal Bands.. Front Immunol, 12 https://doi.org/10.3389/fimmu.2021.811351
Abstract
BACKGROUND: Inclusion of cerebrospinal fluid (CSF) oligoclonal IgG bands (OCGB) in the revised McDonald criteria increases the sensitivity of diagnosis when dissemination in time (DIT) cannot be proven. While OCGB negative patients are unlikely to develop clinically definite (CD) MS, OCGB positivity may lead to an erroneous diagnosis in conditions that present similarly, such as neuromyelitis optica spectrum disorders (NMOSD) or neurosarcoidosis. OBJECTIVE: To identify specific, OCGB-complementary, biomarkers to improve diagnostic accuracy in OCGB positive patients. METHODS: We analysed the CSF metabolome and proteome of CDMS (n=41) and confirmed non-MS patients (n=64) comprising a range of CNS conditions routinely encountered in neurology clinics. RESULTS: OCGB discriminated between CDMS and non-MS with high sensitivity (85%), but low specificity (67%), as previously described. Machine learning methods revealed CCN5 levels provide greater accuracy, sensitivity, and specificity than OCGB (79%, +5%; 90%, +5%; and 72%, +5% respectively) while glial fibrillary acidic protein (GFAP) identified CDMS with 100% specificity (+33%). A multiomics approach improved accuracy further to 90% (+16%). CONCLUSION: The measurement of a few additional CSF biomarkers could be used to complement OCGB and improve the specificity of MS diagnosis when clinical and radiological evidence of DIT is absent.
Keywords
Immunology, diagnosis, metabolomics (OMICS), multiple sclerosis (MS), proteomics, oligoclonal band
Identifiers
External DOI: https://doi.org/10.3389/fimmu.2021.811351
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334197
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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