Tracking MS from the Inside Out: New Biomarkers Offer Insight into Diagnosis and Treatment Response

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system (CNS), marked by demyelination and neurodegeneration. Despite significant advances in imaging and clinical diagnostics, the quest for reliable and minimally invasive biomarkers—especially in blood—remains a pressing challenge. In a groundbreaking study published in PNAS, Huang et al. leveraged high-sensitivity proteomics to identify novel cerebrospinal fluid (CSF) and plasma biomarkers associated with MS. This research not only deepens our biological understanding of MS but also brings us closer to better diagnostic and monitoring tools.

The Study: High-Sensitivity Proteomics in Action
Using the Olink proximity extension assay (PEA), a highly sensitive multiplex immunoassay, researchers profiled 92 inflammation-related proteins in CSF and plasma from two well-characterized Swedish cohorts. The study included MS patients (both relapsing-remitting and progressive), healthy controls, individuals with other neurological diseases, and symptomatic controls with suspected MS.

The research aimed to:

Identify diagnostic biomarkers.

Distinguish between MS subtypes.

Correlate biomarkers with disease activity and severity.

Assess biomarker response to treatments like natalizumab and fingolimod.

Key Findings: CSF and Plasma Biomarkers Unveiled
1. Ten Validated CSF Biomarkers
The study identified 10 CSF proteins significantly elevated in MS patients across both cohorts. These include:

IL-12B and CD5 – associated with T-cell activation.

CXCL9 and MIP-1α – chemokines linked to T-helper cell (Th1) responses.

Eotaxin-1 (CCL11) – correlated with disease duration and progression.

Combined, these CSF biomarkers achieved a diagnostic accuracy (AUC = 0.95) comparable to traditional markers like the IgG index and neurofilament light chain (NfL).

2. Two Plasma Biomarkers: OSM and HGF
Notably, oncostatin M (OSM) and hepatocyte growth factor (HGF) were identified as plasma biomarkers that differentiate MS patients from healthy controls. These are particularly important due to the non-invasive nature of blood sampling.

OSM may act at the blood-brain barrier to regulate immune cell entry.

HGF has known neuroprotective effects and may reflect a compensatory response to CNS injury.

Although these markers are not directly linked to CNS inflammation, their expression in peripheral blood offers promising utility in diagnostics and treatment monitoring.

Beyond Diagnosis: Monitoring Disease Activity
Eotaxin-1 (CCL11)
CCL11 levels in both CSF and plasma correlated with disease duration, especially in secondary progressive MS, suggesting its potential as a biomarker of disease course.

CCL20
Associated with disease severity (as measured by the MS severity score), CCL20 could become a valuable tool for stratifying patients based on risk.

Treatment Insights: Biomarker Dynamics Under Therapy
The researchers tracked biomarker changes in response to two MS therapies:

Natalizumab (targets CNS inflammation): reduced inflammatory markers in CSF.

Fingolimod (acts peripherally): reduced inflammation in plasma but had limited CSF effect.

Interestingly, some markers like CD5 and IL12B decreased in both compartments, showing biomarkers can reflect compartment-specific treatment effects, which may inform therapy selection and monitoring.

Implications and Future Directions
This study represents one of the most comprehensive attempts to discover blood-based MS biomarkers using next-generation proteomics. The dual-cohort validation adds robustness to the findings, making several of these biomarkers strong candidates for clinical translation. Key Takeaways:
Reliable plasma biomarkers for MS (e.g., OSM, HGF) are now within reach. Biomarkers like CCL11 and CCL20 may help predict disease progression and severity. Treatment-specific biomarker changes can help tailor therapies to individual patients. Caveats and Considerations
While promising, the authors stress that further validation in broader and more diverse populations is needed. Additionally, technical sensitivity to sample handling—especially for plasma—highlights the importance of rigorous protocols in biomarker research. Conclusion: A Step Closer to Precision Medicine in MS
Huang et al.'s study marks a significant leap forward in MS research, offering a new suite of biomarkers that could revolutionize early diagnosis, disease monitoring, and treatment personalization. With further validation, these findings could pave the way for more precise, less invasive MS management strategies, ultimately improving outcomes for patients worldwide. Disclaimer: This blog post is based on the provided research article and is intended for informational purposes only. It is not intended to provide medical advice. Please consult with a healthcare professional for any health concerns.

References:
Huang, J., Khademi, M., Fugger, L., Lindhe, Ö., Novakova, L., Axelsson, M., ... & Kockum, I. (2020). Inflammation-related plasma and CSF biomarkers for multiple sclerosis. Proceedings of the National Academy of Sciences, 117(23), 12952-12960.