Fig. 4.

Epitope clusters A and B predict MS with ON onset at high diagnostic accuracy in validation cohorts. a) Validation of epitopes of clusters A and B by MVA confirmed the diagnostic power of these as two blood-based biomarkers to detect MS with ON onset. Box plot analysis of immunoreactivity values of clusters A and B epitopes as obtained by MVA in sera samples of MS with ON onset (samples of ON^MS and MS^ON, n = 20) and controls. y-axes - peptide abundance (in log₁₀); x-axes –study cohorts; p- ANOVA on log-transformed data p value, *- p<0.05, ***- p<0.001. b) High immunoreactivity to epitopes of clusters A and B in sera was always co-detected with high immunoreactivity in CSF. Pearson correlation analysis of ELISPOT values of gB CMV (cluster A) and VCA p18 of EBV (cluster B) in the CSF samples of MS^ON and MS^other patients (n = 20) upon normalisation to total IgG amount. y-axes - ELISPOT values in CSF; x-axes – ELISPOT values in serum; r - correlation coefficient; p - correlation significance level (t-Test). c) ROC analysis data of the predictive value of clusters A and B epitope biomarkers in different validation groups – MS with ON onset (samples of ON^MS and MS^ON, n = 20; Table 1-2), healthy (CTRL samples from discovery cohort (n = 27) and samples from external cohorts of healthy individuals (n = 256) and subjects with non-demyelinating diseases (n = 192; Table 2). Accuracy – balanced accuracy of sensitivity and specificity; area under the curve (AUC).