Multivariate Analysis of Serum Proteins Enhances Detection of Multiple Sclerosis Disease Activity

Multiple Sclerosis (MS) is a complex immune-mediated neurodegenerative disease where the body's immune system mistakenly attacks the protective covering of nerve fibers, leading to a variety of symptoms. It is a chronic inflammatory and demyelinating disease of the central nervous system. While the exact causes of MS are still being researched, it is understood that both inflammation and nerve damage (neurodegeneration) play a role. A new study has identified a panel of proteins in the blood that could help doctors to monitor MS disease activity, which could lead to more personalized and effective treatment plans.

The Challenge of MS
One of the difficulties in managing MS is its unpredictable nature. The disease can vary significantly from person to person, with different rates of progression and different types of symptoms. Currently, doctors rely on tools like MRI scans to detect brain lesions and clinical assessments to track the course of the disease. However, these methods have limitations, including the fact that they may not capture the full picture of what's happening in the body.

Looking for Biomarkers in Blood
Scientists have been searching for “biomarkers” – measurable substances in the body that can indicate a disease or condition. Blood tests are a convenient way to look for these biomarkers, and there is a growing interest in using blood tests to monitor MS. One promising biomarker that has been studied extensively is a protein called neurofilament light chain (NfL). NfL is released when nerve cells are damaged, and higher levels of NfL in the blood have been linked to nerve damage in MS. However, NfL alone may not be sensitive or specific enough to fully capture the complexities of the disease process. NfL is only marginally elevated during relapse, and can be elevated in other neurodegenerative conditions besides MS.

A More Comprehensive Approach
In this study, researchers looked at over 1100 different proteins in the blood of more than 600 people with MS. They used advanced techniques to identify a panel of 20 proteins that were strongly linked to MS disease activity. This "custom assay panel" (CAP) includes proteins involved in inflammation, immune response, and nerve damage. The study looked at three measures of MS activity:

* Gadolinium-enhancing (Gd+) lesions: These lesions, detected by MRI, indicate active inflammation in the brain.
* Clinical Relapses: These are episodes of worsening MS symptoms.
* Annualized Relapse Rate (ARR): The frequency of relapses experienced by a patient over a year.

Key Findings
The study found that: * NfL is important but not the whole story: As expected, NfL was strongly associated with MS disease activity. However, the researchers found that looking at a combination of 20 proteins, rather than just NfL, could predict MS activity more accurately.

* Multivariate models outperform univariate analysis: Combining multiple proteins into a model using machine learning was much better at predicting MS disease activity than using NfL alone. Multivariate modeling significantly outperformed univariate NfL to predict gadolinium lesion activity, clinical relapse status and annualized relapse rate.

* The model works even without NfL: Even when the researchers took NfL out of the equation, they found that the remaining 19 proteins could still predict MS activity, which suggests that these other proteins are contributing important information about the disease process.

* The proteins provide insight into the biology of MS: The researchers found that the 20 proteins in the panel were linked to specific biological processes known to be involved in MS, such as inflammation and nerve cell damage.

* The model can capture different aspects of MS: The multi-protein panel is able to capture different aspects of MS, providing a more complete picture of a patient’s disease.

What does this mean for people with MS?
This research is still in its early stages, but it has the potential to significantly improve the way MS is managed. A blood test that can accurately track MS activity could have several benefits:

* More accurate diagnosis of relapses: The test could help doctors distinguish between true relapses and other conditions or stressors that cause similar symptoms.

* Prediction of relapses: The test might be able to identify an impending relapse even before the patient experiences symptoms.

* Monitoring treatment effectiveness: The test could allow doctors to quickly assess whether a treatment is working, and adjust treatment plans if needed.

* Personalized treatment: By tracking individual patient's MS activity over time, the test could help tailor treatment plans to the specific needs of each person.

Looking Ahead
This study is an important step forward in the development of blood-based tests for MS. The researchers note that further studies are needed to validate these findings in larger groups of people, as well as to evaluate the test's ability to track MS progression over time. The goal is to develop a clinically validated test that can be used to personalize MS care and improve outcomes for people living with this challenging disease. This test has the potential to identify active relapse, predict impending relapse, confirm no evidence of disease activity (NEDA) status, assess patient-specific changes, and assess response to disease modifying therapies.

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:
Chitnis, T., Qureshi, F., Gehman, V. M., Becich, M., Bove, R., Cree, B. A., ... & Baranzini, S. E. (2023). Inflammatory and neurodegenerative serum protein biomarkers increase sensitivity to detect disease activity in multiple sclerosis. medRxiv, 2023-06.