AUTHOR=Probert Fay , Yeo Tianrong , Zhou Yifan , Sealey Megan , Arora Siddharth , Palace Jacqueline , Claridge Timothy D. W. , Hillenbrand Rainer , Oechtering Johanna , Kuhle Jens , Leppert David , Anthony Daniel C. TITLE=Determination of CSF GFAP, CCN5, and vWF Levels Enhances the Diagnostic Accuracy of Clinically Defined MS From Non-MS Patients With CSF Oligoclonal Bands JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2022 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.811351 DOI=10.3389/fimmu.2021.811351 ISSN=1664-3224 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.