Table 1.
Epidemiological and clinical characteristics of multiple sclerosis patients included in the study.
Table 2.
Biomarkers that discriminate between Relapsing-Remitting and Progressive Clinical forms of MS by ROC curves.
Table 3.
HGF, Eotaxin/CCL11, MCP-1/CCL2, Rantes/CCL5, EGF and MIP-1β/CCL4 comparison in the test and validation cohorts.
Fig 1.
Different plasma levels of HGF, Eotaxin/CCL11, MCP-1/CCL2 and Rantes/CCL5 in MS clinical forms.
Plasma levels of HGF, Eotaxin/CCL11, MCP-1/CCL2 and Rantes/CCL5 were lower in relapsing-remitting MS than in the progressive MS patients. Comparison of the plasma levels of HGF, Eotaxin/CCL11 (top dot plots), MCP-1/CCL2 and Rantes/CCL5 (lower dot plots) in relapsing-remitting (RR-MS, n = 80) and in the group of progressive MS (n = 49) patients. Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values. Note that the Relapsing-remitting group comprises the clinical groups: RR-MS Remission, RR-MS Active, RESPONDERS, NON RESPONDERS and RELAPSES. The Progressive group comprises Secondary (SP-MS) and Primary-progressive patients.
Fig 2.
Different plasma levels of EGF and MIP-1β/CCL4 in MS clinical forms.
Plasma levels of EGF and MIP-1β/CCL4 were lower in the progressive MS than in relapsing-remitting MS patients. Comparison of the plasma levels of EGF and MIP-1β/CCL4 between patients with relapsing-remitting (RR-MS, n = 80) and in progressive MS patients (n = 49). Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values. Note that the Relapsing-remitting group comprises the clinical groups: RR-MS Remission, RR-MS Active, RESPONDERS, NON RESPONDERS and RELAPSES. The Progressive group comprises Secondary (SP-MS) and Primary-progressive patients.
Table 4.
Logistic regression with HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4 as independent variables and the clinical MS-forms (Relapsing-Remitting vs Progressive MS) as the dichotomous target variable.
Table 5.
Clinical utility of HGF, Eotaxin/CCL11, EGF and MIP-1β/CCL4 as MS biomarkers and clinical utlity of their combination in a model by multivariate logistic regression analysis.
Fig 3.
FGFb levels were significantly decreased in primary progressive MS patients.
Comparison of the plasma levels of FGFb between primary progressive MS patients (PP-MS, n = 18) with respect to healthy controls (HC, n = 36), to secondary progressive MS patients (SP-MS, n = 31) and to patients undergoing a clinical relapse (RELAPSES, n = 11). Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values.
Fig 4.
VEGF levels were significantly higher in secondary progressive MS patients.
Plasma levels of the vascular growth factor (VEGF) in the validation cohort, were higher in secondary progressive MS patients (SP-MS, n = 16) than in patients with the relapsing-remitting form (RR-MS, n = 38) and than in healthy controls (HC, n = 20). The SP-MS patients had higher plasma levels of VEGF than primary progressive MS patients (PP-MS, n = 9) but this difference did not reach statistical significance. Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values.
Fig 5.
IP10/CXCL10 and MCP-1/CCL2 levels were higher in MS patients with good response to IFN-β treatment.
Long-term IFN-β treated RR-MS patients (RESPONDERS, n = 20) presented with higher circulating levels of IP10/CXCL10 and MCP-1/CCL2 than non responders to IFN-β (NON RESPONDERS, n = 13). Mann—Whitney statistical test was used for calculation of the reported p-value; median values are represented by a gray bar; individual dots indicate single donor values.
Fig 6.
Plasma biomarkers regulations in our MS clinical forms.
The combinations of biomarkers were down or up-regulated simultaneously in the individuals. The results are represented with a box and whiskers graph. The bottom and top of the box represent the first and third quartiles, the median values are represented by the line inside the box and the ends of the whiskers represent the minimum and maximum of the values. Biomarkers from Relapsing-remitting MS patients are represented with an R, secondary-progressive MS patients are represented with and S and primary-progressive MS patients are represented with a P. Note that the Relapsing-remitting group comprises the clinical groups: RR-MS Remission, RR-MS Active, RESPONDERS, NON RESPONDERS and RELAPSES.
Fig 7.
Plasma biomarkers significant across our MS clinical forms.
Findings are summarized. Listed biomarkers were found to differ significantly between comparison groups. Arrow preceding each biomarker name indicates increase or decreased plasma concentrations in MS groups.