The number of peaks with low p-values in the comparison of the two MScl types is lower than the number of background peaks, so this is a strong indication that, even though there may be peptides and proteins that are differentially abundant in the comparison, overall the difference between the two disease types appears to be undetectable by means of the univariate analysis. One of the peptides of protein jagged-1 is over three times less abundant in PP MScl and also is observed with a lower incidence in this group ( Table 2) . Protein jagged-1 is a ligand for multiple Notch receptors and involved in the mediation of Notch signaling, which influences neuronal function and development [20] . The Notch signaling pathway has long been known to influence cell fate in the developing nervous system. Jagged-1 has been found to be highly expressed in hypertrophic astrocytes within and around active MScl plaques lacking remyelination, while, in contrast, there was negligible jagged-1 expression in remyelinated lesions suggesting involvement of the Notch pathway in remyelination in MScl [21] . Later, linkage equilibrium screening implicated a number of genes, including the jagged-1 gene, as susceptibility genes for MScl in a large contingent of Europeans [22] . It has also been suggested that jagged-1 has therapeutic potential in the treatment of CD8 + T cell mediated diseases, due to it's ability to deliver indirect negative signals into CD8 + T cells in vivo [23] . Additionally, animal models have shown that elevated expression of Notch and jagged-1 expression does not appear to be a limiting factor in remyelination, but the animal model study reports that there were no quantitative differences in Notch1 expressing cells in slow and rapidly remyelinating lesions, indicating that Notch-Jagged signaling is not a rate-limiting determinant of remyelination in rodent models of demyelination [24] . Additionally immunohistochemistry experiments have shown that constituents of the Notch pathway are expressed in remyelination in an animal model of T-cell-and antibody-mediated CNS demyelination [25] . However, network studies based on the quantitative expression levels of 20 genes in over one hundred individuals identify jagged-1 as a new therapeutic target whose differential behavior in the MScl network was not modified by immunomodulatory therapy, illustrating how network analysis can predict therapeutic targets for immune intervention and identifying the immunomodulatory properties of jagged-1, making it a new therapeutic target for MScl and other autoimmune diseases [26] . The identified peptide of vitamin D-binding protein is not observed in any of the PP MScl samples, but small peaks of this peptide are detected in 6/11 RR MScl samples. Impaired vitamin D homeostasis has been widely implicated in MScl for some years now [27] [28] [29] . This vitamin directly and indirectly regulates the differentiation, activation of CD4+ T-lymphocytes and can prevent the development of autoimmune processes [30, 31] , and so it may be involved MScl. Considering that the geographic incidence of MScl indicates an increase in MScl with a decrease in sunlight exposure, that vitamin D is produced in the skin by solar or UV irradiation and that high serum levels of 25-hydroxyvitamin D have been reported to correlate with a reduced risk of MScl, a protective role of vitamin D has been suggested [32] . More than 99% of 25-hydroxyvitamin D, the principle circulating metabolite of vitamin D is bound to proteins, of which approximately 90% is bound to vitamin D-binding protein [33, 34] . Recently, a CSF proteomics study showed that serum levels of vitamin D-binding protein were decreased significantly in RR MScl patients compared to other neurological disorders [35] . While our results do not indicate a differential abundance difference between the MScl subtypes and the controls, the two disease types did vary significantly in CSF levels of vitamin D-binding protein, with RR MScl showing a higher abundance. Since a neuroprotective function has been suggested for vitamin D, it may be that in PP MScl this neuroprotective pathway is at least partially deficient, resulting in a significantly more disabling disease manifestation. However, it should not be forgotten that vitamin D-binding protein has pleiotropic functions, beyond vitamin D metabolism. It can significantly enhance the chemotactic response to complement fragment C5a [36] , and there are substantial stimulatory effects on macrophages [37] . In light of the increasingly recognized role of innate immunity in the progressive phase of MS pathogenesis [38] , vitamin D-binding protein appears an interesting candidate mediator.