Soluble Biomarkers in MS. Review.
Posted: Mon Apr 21, 2025 11:36 pm
Role of soluble biomarkers in multiple sclerosis
https://www.sciencedirect.com/science/a ... 9025000231
Excerpts:
A large cohort from the United States identified that infection with Epstein-Barr virus (EBV) increased the risk of developing MS by 30-fold, and that it was essentially necessary in order for MS to occur [10]. Also of interest, in the patients who seroconverted to EBV, the ones who later went on to develop MS had higher sNfL levels that those who did not subsequently develop MS, while prior to EBV seroconversion both groups had similar sNfL levels, suggesting that neuroaxonal damage only begins to occur after EBV infection took place.
This cohort was analyzed further, and it was found that sNfL levels can begin to increase as early as 6 years prior to first clinical MS symptoms [11]. Furthermore, emerging data hints at a possible role for EBV-infected B cells in driving MS neuroinflammation through several plausible mechanisms, including a direct role of CNS penetrant EBV infected B cells, dysregulated T and NK responses, and molecular mimicry for example between EBV nuclear antigen 1 (EBNA1) and the glial cell adhesion molecule (GlialCAM) [12,13].
This suggests that even during a “prodromal period” before typical symptoms of MS arise, soluble biomarkers may be useful in identifying patients who have the MS pathophysiology already underway, and thus may benefit from treatment.
Future of soluble biomarkers
Soluble biomarkers are revolutionizing the management of MS. Over the past eight years, advancements in highly sensitive analytical platforms, such as SIMOA, have enabled the reliable quantification of protein biomarkers in blood samples. sNfL exemplifies this progress, achieving FDA breakthrough device status on multiple platforms (Roche, Quanterix, Siemens Healthineers). sNfL has been implemented as an outcome measure in clinical trials, leading to regulatory approvals [142], and is increasingly adopted in routine clinical care. While soluble biomarkers have the potential to be vital in precision medicine for MS, their widespread implementation requires addressing technical, systemic, and patient-centric challenges.
The integration of multiple biomarkers is pivotal for capturing the heterogeneity of MS, encompassing both inflammatory and non-inflammatory injury. Combining NfL (a proxy for relapsing pathophysiology) with GFAP (a marker of non-relapsing, progressive biology) has demonstrated prognostic superiority compared to either marker alone [30,43,60]. Moreover, CD40 ligand, a key mediator of T-B cell interactions, holds a dual role as a blood and CSF biomarker of lymphocyte activation linked to MS disease activity and as a promising therapeutic target
https://www.sciencedirect.com/science/a ... 9025000231
Excerpts:
A large cohort from the United States identified that infection with Epstein-Barr virus (EBV) increased the risk of developing MS by 30-fold, and that it was essentially necessary in order for MS to occur [10]. Also of interest, in the patients who seroconverted to EBV, the ones who later went on to develop MS had higher sNfL levels that those who did not subsequently develop MS, while prior to EBV seroconversion both groups had similar sNfL levels, suggesting that neuroaxonal damage only begins to occur after EBV infection took place.
This cohort was analyzed further, and it was found that sNfL levels can begin to increase as early as 6 years prior to first clinical MS symptoms [11]. Furthermore, emerging data hints at a possible role for EBV-infected B cells in driving MS neuroinflammation through several plausible mechanisms, including a direct role of CNS penetrant EBV infected B cells, dysregulated T and NK responses, and molecular mimicry for example between EBV nuclear antigen 1 (EBNA1) and the glial cell adhesion molecule (GlialCAM) [12,13].
This suggests that even during a “prodromal period” before typical symptoms of MS arise, soluble biomarkers may be useful in identifying patients who have the MS pathophysiology already underway, and thus may benefit from treatment.
Future of soluble biomarkers
Soluble biomarkers are revolutionizing the management of MS. Over the past eight years, advancements in highly sensitive analytical platforms, such as SIMOA, have enabled the reliable quantification of protein biomarkers in blood samples. sNfL exemplifies this progress, achieving FDA breakthrough device status on multiple platforms (Roche, Quanterix, Siemens Healthineers). sNfL has been implemented as an outcome measure in clinical trials, leading to regulatory approvals [142], and is increasingly adopted in routine clinical care. While soluble biomarkers have the potential to be vital in precision medicine for MS, their widespread implementation requires addressing technical, systemic, and patient-centric challenges.
The integration of multiple biomarkers is pivotal for capturing the heterogeneity of MS, encompassing both inflammatory and non-inflammatory injury. Combining NfL (a proxy for relapsing pathophysiology) with GFAP (a marker of non-relapsing, progressive biology) has demonstrated prognostic superiority compared to either marker alone [30,43,60]. Moreover, CD40 ligand, a key mediator of T-B cell interactions, holds a dual role as a blood and CSF biomarker of lymphocyte activation linked to MS disease activity and as a promising therapeutic target