Table 5.
Biomarkers of Immunomodulation and Inflammation.
| Potential Biomarker | Study Population (n) | Sample | Results | Possible Utility |
|---|---|---|---|---|
| Cytokines | RRMS (114), CIS (43) | Serum | Immunologically distinct subgroups of MS, and these subgroups may stratify treatment response to IFN-β [6] | Predictive, prognostic, treatment response |
| Pediatric onset MS (40), controls (11) | Serum | IL-10 is predictive of relapse [94] | ||
| RRMS (323), SPMS (40), PPMS (24), CIS (79), OIND (176), ONIND (181), controls (14) | CSF | CXCL13 has been found to be correlated with worse prognosis and exacerbations in RRMS and conversion of CIS to MS [95] | ||
| MS (136), OND (35), controls (49) | CSF, plasma | Plasma and CSF levels of CCL11 is associated with disease duration, especially in patients with SPMS; CCL20 is associated with disease severity and CSF levels of IL-12B, MIP-1a, CD5, and CXCL9, and plasma levels of OSM and HGF to be associated with MS [96] | ||
| RRMS (39), controls (39) | Serum | IL-6 has been found to be correlated with age of onset for MS patients and is detected at a higher rate in MS patients compared to controls [97] | ||
| sCD40L | RRMS (8), SPMS (32), BMS (12), controls (5) | Plasma | Significantly elevated in SPMS compared to BMS and RRMS; MCP1/CCL2 and sCD40L can be used together to differentiate between RRMS and SPMS; IFN-γ and sCD40L can be used together to differentiate between BMS and SPMS [99] | Prognostic |
| CHI3L1 | RRMS (38), progressive MS (16), CIS (40), controls (29) | CSF, serum | Strong expression in MS patients, especially astrocytes and microglia in white matter plaques. Increased with disease stage and associated with more rapid conversion to RRMS in CIS patients. Lower CSF levels in progressive MS compared to RRMS [102] | Predictive, prognostic, treatment response |
| RRMS (124), SPMS (30), PPMS (66), controls (57) | Plasma | Increased in patients with progressive MS compared to patients with RRMS and healthy controls; higher levels were associated with more relapses and T1 and T2-weighted lesion load and brain parenchyma fraction in patients with MS [103] | ||
| CIS (84) | CSF | Higher levels associated with quicker disease conversion to clinically defined MS in CIS patients [104] | ||
| RRMS (117) | Serum | Increased in groups of patients unresponsive to IFN-β treatment [105] | ||
| HSP | MS (191), controls (365) | Whole blood | Expression of HSPA1L gene that encodes for HSP70-hom protein was correlated with increased risk of MS development; increased expression of HSP70-hom protein was correlated with disease severity [111] | Prognostic, treatment response |
| RRMS (40), SPMS (19), PPMS (9), CIS (26), OIND (28), ONIND (41), controls (114) | Serum | Higher HSP70 levels in MS compared to healthy controls but lower than other inflammatory neurological diseases; Increased HSP70 levels in CIS and RRMS compared to PPMS or SPMS [112] | ||
| Steroid-resistant MS (15), steroid-sensitive MS (15) | Peripheral blood | Increased HSP90 in the glucocorticoid receptor complex of patients that are steroid-resistance compared to those that are steroid-sensitive [114] | ||
| KFLC | RRMS (37), PPMS (4), OND (368) | CSF, serum | Increased in MS patients [116] | Predictive, prognostic |
| RRMS (23), SPMS (28), PPMS (6) | CSF | Correlated with future disability [117] | ||
| CIS (78), controls (25) | CSF | CIS patients with higher CSF levels of KFLC had earlier conversion to clinical defined MS [118] | ||
| HERVs | MSRV+ MS (10), MSRV- MS (8) | CSF | MSRV+ MS patients had higher EDSS scores compared to MSRV- MS patients at 6-year follow-up. MSRV+ MS patients have a higher annual relapse rate. Two patients in the MSRV+ group developed the progressive form of MS [120]. | Prognostic |
| Uric Acid | MS (124), OND (124) | Serum | Uric acid levels are decreased in MS patients compared to those with other neurological diseases. No correlation was found between urate levels and disease activity, duration, disability, or course [121] | Associated marker |
| MS (61,667), controls (86,806) | Serum | Increased urate levels do not lead to an increased risk of developing MS [122] |
CHI3L1 = Chitinase-3-Like-1 Precursor; HSP = heat shock protein; KFLC = kappa free light chain; HERVs = human endogenous retroviruses; OND = other neurological diseases; OIND = other inflammatory neurological diseases; ONIND = other non-inflammatory neurological diseases; BMS = benign multiple sclerosis; MSRV = MS-associated retrovirus; IL = interleukin; CCL = C-C motif chemokine ligand; MIP = macrophage inflammatory protein; CD = cluster of differentiation; OSM = oncostatin; HGF = hepatocyte growth factor; MCP = monocyte chemoattractant protein.