Table 1 Description of candidate biomarkers studied in this cohort
From: Combination protein biomarkers predict multiple sclerosis diagnosis and outcomes
Marker | Description | Evidence for relevance in multiple sclerosis |
|---|---|---|
CXCL12 | Chemokine/cytokine-related | Increased in CSF of people with PPMS vs RRMS [48], increased in people with multiple sclerosis vs controls [49] |
CXCL13 | Chemokine/cytokine-related | Increased in CSF of people with multiple sclerosis and correlated with relapse rate [50] |
IL-6 | Chemokine/cytokine-related | Increased in CSF of people with multiple sclerosis, and correlated with disease activity in RRMS [51] |
IL-10 | Chemokine/cytokine-related | Decreased in people with CIS who relapsed [52]. In multiple sclerosis, low IL-10 was associated with higher disability [53], and high IL10 with inactive disease [54] |
IL-12/IL-23p40 | Chemokine/cytokine-related | Found upregulated in multiple sclerosis serum [55] and is higher in people with RRMS vs controls [54] |
Soluble CD27 | Chemokine/cytokine-related | Increased levels of the soluble CD27 are found in CSF of people with multiple sclerosis, and there is a correlation between IgG index and CD27[32] |
CRP | Inflammatory marker | Serum CRP/albumin ratio are correlated with higher multiple sclerosis disease activity and relapses [56], as well multiple sclerosis disease subtype[57], whereas serum CRP can predict depressive symptoms in newly diagnosed people with multiple sclerosis [58] |
GFAP | CNS marker | CSF GFAP has been found to be higher in people with CIS/RRMS versus controls [59]. GFAP levels in serum and CSF have been linked with disease duration and severity, respectively [60] |
CHi3L1 | CNS marker | CSF chitinase-3-like-1 has been found to be predictive of conversion from CIS to multiple sclerosis [10]. CSF and serum chitinase-3-like-1 were both increased in more advanced multiple sclerosis [61] |
Osteopontin | Chemokine/cytokine-related | Osteopontin levels in CSF have been found to be associated with disease activity [11] and disease progression [62], and were found increased in the CSF of people with multiple sclerosis vs controls [63] |
TGF-β | CNS marker | CSF levels of TGF-β were higher in people with active multiple sclerosis [64], while lower TGF-β was found in the blood of people with multiple sclerosis when compared to controls [65] |
MCP-1 | Chemokine/cytokine-related | MCP-1 levels were decreased in the CSF of multiple sclerosis patients when compared to controls [29, 66] |
BDNF | CNS marker | BDNF levels were decreased in the blood of people with multiple sclerosis vs controls, and lower in people with SP multiple sclerosis than RR multiple sclerosis[67] |
IL-4 | Chemokine/cytokine-related | Serum and CSF IL-4 was found to be increased in people with multiple sclerosis vs controls [68,69,70] |
CCL27 | Chemokine/cytokine-related | Serum CCL27 levels were higher in newly diagnosed and acute multiple sclerosis cases [30] |
IFNγ | Chemokine/cytokine-related | In multiple sclerosis, blood levels of IFNγ were increased prior to the manifestation of symptoms [71] |
IL-8 | Chemokine/cytokine-related | CSF levels of IL-8 were found to be significantly higher in people with multiple sclerosis vs controls, but the serum levels were lower in people with multiple sclerosis vs controls [72] |
TNFr1 (s) | Chemokine/cytokine-related | CSF levels of soluble TNFr1 were higher in people with multiple sclerosis vs controls, and were also associated with disease burden (lesion volume) [73] |
TNFα | Chemokine/cytokine-related | Serum TNFα levels correlated with disease activity in RRMS [54] and was found higher in people with multiple sclerosis versus healthy controls [74] |
IL-18 | Chemokine/cytokine-related | Serum IL-18 was found to be higher in people with multiple sclerosis vs controls, higher in SPMS compared to RRMS, and higher during relapses [75] |
Vitamin D binding protein | Metabolic marker | Serum from people with multiple sclerosis had high levels of DBP [76], however a different study found the opposite for newly diagnosed patients [37] |
LIF | Chemokine/cytokine-related | CSF and serum LIF levels were higher in people with multiple sclerosis vs controls [77] |
Complement proteins TCC, iC3b, C3, C5, C9, fH, fB, fI, C1inh/C1s complex | Immune system | Several complement system components and proteins have been found to be altered in CIS and multiple sclerosis, e.g. C3, C4, C4a, C1inhibitor and Factor H were found increased in the plasma of people with multiple sclerosis, whereas C9 was found decreased [78]. A study focusing on disease progression and response to treatment identified C4a and C3 as potential biomarkers of disease progression and subtype [79]. One study found C4b to be elevated in multiple sclerosis [80] |
Neurofilament-light | CNS marker | Although less sensitive when measured in blood [81] several studies have found neurofilament light to be a predictive and diagnostic biomarker in multiple sclerosis (significantly higher in multiple sclerosis vs controls), higher in people with progressive vs RRMS, as well as in people with concurrent disease activity vs people in remission. Data are summarised in a recent systematic review and meta-analysis [82] |