Table 1.
Biomarkers and their characteristics.
Fig 1.
Macrophages and microglia and the suggested roles of sCD163, CXCL13, NEO, NfL, OPN, and IgG in MS pathology.
Fig 1 shows the biomarkers sCD163, CXCL13, NEO, NfL and OPN and their relation to monocyte activation, macrophage migration, and interactions with macrophages/microglia in active (acute/chronic) MS lesions. Biomarker characteristics are listed below: Abbreviations: sCD163 (soluble CD163), mCD163 (membrane bound CD163), NEO (neopterin), NfL (neurofilament light polypeptide), OPN (osteopontin), Th-cells (T helper cells), MS (multiple sclerosis), CSF (cerebrospinal fluid), EC (epithelial cell), Ag (antigen), SC (Schwann cell), OND (other neurological disease), ROS (reactive oxygen species).
Table 2.
Demographic and clinical data of the patients with MS/CIS and SC.
Fig 2.
Box plots of sCD163, CXCL13, NEO, NfL, and OPN.
Fig 2 shows box plots of all biomarkers including CSF and serum concentrations as well as ratios and index values. The box plots show levels of all the parameters for each group, RRMS, PPMS, CIS and SC. The horizontal line in each box is the median, whiskers fences the upper and lower quartiles. The data on sCD163 have previously been presented in [18]. Fig 2a–2d shows the values for sCD163, Fig 2e–2h shows the values for CXCL13, Fig 2i–2l shows the values for NEO, Fig 2m shows the values for NfL CSF, and Fig 2n–2qshows the values for OPN. For all biomarkers, there were some overlaps in levels between patient groups, and symptomatic controls. Abbreviations: RRMS (relapsing-remitting MS), PPMS (primary-progressive MS), CIS (clinically isolated syndrome), SC (symptomatic controls), CSF (cerebrospinal fluid), sCD163 (soluble CD163), NEO (neopterin), NfL (neurofilament light polypeptide), OPN (osteopontin).
Table 3.
Median levels and range of biomarkers in serum and CSF samples as determined by ELISA, for the patient groups.
Table 4.
Spearman Correlation on categorical, nominal data and Pearson correlation on continuous data.
Table 5.
Pearson pairwise correlation analysis without and with the Bonferroni correction of biomarkers: sCD163, CXCL13, NEO, NfL, and OPN.
Table 6.
Results from linear regression analyses of differences in levels of biomarkers between patients with MS/CIS and SC.
Fig 3.
Fig 3 shows the biomarker profile for each group of patients.
The biomarker profile was constructed as an overview representing the major characteristics of each group in the cohort. The profile was determined by categorizing the GM levels of the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the NfL CSF, the OPN serum, and the IgG index for each patient group in the following manner: Very high (significantly increased GM, p <0.001); High (significantly increased GM, p <0.01); Moderate (significantly increased GM, p <0.05); Low (zero is included in the CI). Abbreviations: NEO (neopterin), NfL (neurofilament light polypeptide), OPN (osteopontin), SC (symptomatic controls), RRMS (relapsing-remitting MS), PPMS (primary-progressive MS), CIS (clinically isolated syndrome), CI (confidence interval), GM (geometric means).
Fig 4.
ROC curves for the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the NfL CSF, the OPN serum, and the IgG index.
Fig 4 shows the ROC curves generated for the sCD163 ratio (4a), the CXCL13 ratio (4b), the NEO ratio (4c), the NfL CSF (4d), the OPN serum (4e), and the IgG index (4f). The data on sCD163 have previously been presented in [18]. AUC, with 95% CI, is given for each parameter. The parameter results for patients with RRMS, PPMS, and CIS are combined as true positives and plotted against SC as true negatives. The diagonal dividing the ROC space represents the random event. Abbreviations: ROC (receiver operating characteristic), AUC (area under the curve), RRMS (relapsing-remitting MS), PPMS (primary-progressive MS), CIS (clinically isolated syndrome), SC (symptomatic controls), CSF (cerebrospinal fluid), CI (confidence interval).
Fig 5.
ROC curves for the sCD163 ratio, the CXCL13 ratio, the NEO ratio, the NfL index, and the OPN serum combined with the IgG index individually as well as a combined ROC curve.
Fig 5 shows the combined ROC curves generated for the IgG index and the sCD163 ratio (5a), the CXCL13 ratio (5b), the NEO ratio (5c), the NfL CSF (5d), the OPN serum (5e), and All biomarkers (5f). AUC, with 95% CI, is given for each parameter. The parameter results for patients with RRMS, PPMS, and CIS are combined as true positives and plotted against SC as true negatives. The diagonal dividing the ROC space represents the random event. Abbreviations: ROC (receiver operating characteristic), AUC (area under the curve), RRMS (relapsing-remitting MS), PPMS (primary-progressive MS), CIS (clinically isolated syndrome), SC (symptomatic controls), CI (confidence interval).