Decoding the Blood: How Gene Signatures Could Personalize MS Treatment
Imagine if your blood could tell doctors how well your multiple sclerosis (MS) treatment is working—or even predict which therapy is right for you. Thanks to cutting-edge research in molecular immunology, this possibility is closer than ever.
A team of researchers from the Neurological Institute “Carlo Besta” in Milan, Italy, led by Chiara Cordiglieri and Renato Mantegazza, has identified a promising gene expression signature in the blood of MS patients undergoing treatment. Their findings, published in Clinical Immunology, shed light on how different disease-modifying therapies (DMTs) shape immune responses at the genetic level, potentially paving the way for more personalized and effective care in relapsing-remitting MS (RR-MS).
MS: A Complex Puzzle in Need of Better Tools
Multiple sclerosis is a chronic autoimmune disease in which the immune system mistakenly attacks the protective covering of nerve fibers in the central nervous system. While we have a growing arsenal of therapies that can reduce inflammation and slow disease progression, many patients respond differently to the same treatment—and clinicians still lack reliable biomarkers to guide therapeutic decisions.
Currently, diagnosis and monitoring rely heavily on clinical symptoms and MRI scans. The promise of blood-based biomarkers lies in their accessibility and potential to provide a real-time snapshot of immune activity. That’s exactly what this study set out to explore.
The Quest: Can Gene Expression Reveal Treatment Effectiveness?
The researchers focused on a cohort of 78 patients with RR-MS, comparing gene activity in their blood before and after treatment with three different DMTs: glatiramer acetate (GA), interferon-beta (IFNβ), and fingolimod. They began with a discovery phase, using microarrays to scan the entire transcriptome—the full set of RNA messages transcribed from DNA—in treated and untreated patients.
From this vast dataset, they identified eight genes that consistently changed in response to treatment:
ITGA2B, ITGB3: Involved in cell adhesion and platelet function
CD177: Related to neutrophil activity
IGJ: A marker for plasma B cells
IL5RA: Part of the interleukin-5 receptor, important in immune signaling
MMP8: A metalloproteinase involved in tissue remodeling
P2RY12: A purinergic receptor linked to immune regulation
S100β: A calcium-binding protein typically associated with brain injury
All genes—except S100β—were downregulated after therapy, while S100β was consistently upregulated, hinting at its complex role in immune regulation.
Why These Eight Genes Matter
Each of these genes plays a role in the immune response, from how white blood cells move through the body to how they communicate and mature. For example, ITGA2B and ITGB3 are part of integrins that help immune cells migrate into the brain—an essential step in MS pathology. By showing reduced expression after treatment, the data suggest these therapies help "cool down" the immune system’s aggressiveness.
Interestingly, the upregulation of S100β, typically seen as a marker of CNS damage, was observed across all therapies. This might seem paradoxical—but in peripheral immune cells, S100β could serve a different, potentially regulatory, function. The study even found increased levels of S100β in certain regulatory immune cells, like Tregs and B cells, suggesting it may contribute to a more balanced immune state.
A Step Toward Tailored Treatment
What makes this research stand out is its longitudinal design. By following patients over a year and taking samples at multiple time points, the scientists could observe how gene expression evolved with treatment—offering dynamic insights rather than a single snapshot.
The team also validated their findings at the protein level using flow cytometry, adding another layer of confidence to their results. For instance, they observed decreases in immune cells expressing CD177, IL5RA, and integrin subunits, aligning with the mRNA trends.
Importantly, each therapy had its own unique signature:
GA led to a broad downregulation of genes linked to immune migration and inflammation.
IFNβ had a milder impact, notably failing to reduce MMP8 and IL5RA.
Fingolimod, a second-line therapy, showed a distinct effect, particularly on CD8+ T cells and S100β expression.
Where Do We Go From Here?
While this study is exploratory, it’s a significant leap forward. The eight-gene signature offers a potential tool for tracking treatment response, and perhaps even predicting which drug a patient is most likely to benefit from.
Before these findings can be translated into clinical tests, they need to be validated in larger, diverse patient populations. But the potential is enormous: a simple blood test could help neurologists personalize MS treatment, reduce trial-and-error prescribing, and monitor effectiveness more precisely.
Bottom Line
This research brings us closer to the holy grail of MS care: personalized, data-driven treatment. By decoding the molecular “fingerprints” of DMTs in the blood, scientists are giving clinicians a powerful new lens to look through—one that could help transform the lives of patients navigating this complex disease.
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:
Cordiglieri, C., Baggi, F., Bernasconi, P., Kapetis, D., Faggiani, E., Consonni, A., ... & Mantegazza, R. (2016). Identification of a gene expression signature in peripheral blood of multiple sclerosis patients treated with disease-modifying therapies. Clinical Immunology, 173, 133-146.
