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Journal article

Determination of CSF GFAP, CCN5, and vWF levels enhances the diagnostic accuracy of clinically defined MS from non-MS patients with CSF oligoclonal bands

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.

Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.3389/fimmu.2021.811351

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Role:
Author
ORCID:
0000-0002-8580-2023
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pharmacology
Role:
Author
More by this author
Institution:
University of Oxford
Division:
SSD
Department:
Said Business School
Role:
Author
ORCID:
0000-0001-6499-6941


More from this funder
Funder identifier:
https://ror.org/03x94j517
Grant:
MC_PC_15029
More from this funder
Funder identifier:
https://ror.org/043fwdk81
Grant:
59


Publisher:
Frontiers
Journal:
Frontiers in Immunology More from this journal
Volume:
12
Article number:
811351
Place of publication:
Switzerland
Publication date:
2022-02-04
Acceptance date:
2021-12-27
DOI:
EISSN:
1664-3224
Pmid:
35185866


Language:
English
Keywords:
Pubs id:
1241257
Local pid:
pubs:1241257
Deposit date:
2024-09-05

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