# Multiple sclerosis disease activity, a multi-biomarker score of disease activity and response to treatment in multiple sclerosis

**Authors:** Alexandru Tatomir, Freidrich Anselmo, Dallas Boodhoo, Hegang Chen, Armugam P. Mekala, Vinh Nguyen, Jacob Cuevas, Violeta Rus, Horea Rus

PMC · DOI: 10.3389/fimmu.2024.1338585 · Frontiers in Immunology · 2024-06-27

## TL;DR

This study introduces a multi-biomarker score to assess disease activity and treatment response in multiple sclerosis patients.

## Contribution

A novel multi-biomarker score (MSDA) is developed to predict relapses and treatment response in multiple sclerosis.

## Key findings

- The MSDA score using four or six biomarkers showed high sensitivity and specificity.
- MSDA scores correlated with the Expanded Disability Status Scale (EDSS).
- The MSDA test may help monitor treatment response in multiple sclerosis patients.

## Abstract

Regular assessment of disease activity in relapsing-remitting multiple sclerosis (RRMS) is required to optimize clinical outcomes. Biomarkers can be a valuable tool for measuring disease activity in multiple sclerosis (MS) if they reflect the pathological processes underlying MS pathogenicity. In this pilot study, we combined multiple biomarkers previously analyzed in RRMS patients into an MS disease activity (MSDA) score to evaluate their ability to predict relapses and treatment response to glatiramer acetate (GA). Response Gene to Complement 32 (RGC-32), FasL, IL-21, SIRT1, phosphorylated SIRT1 (p-SIRT1), and JNK1 p54 levels were used to generate cut-off values for each biomarker. Any value below the cutoff for RGC-32, FasL SIRT1, or p-SIRT1 or above the cutoff for IL-21 or JNK1 p54 was given a +1 value, indicating relapse or lack of response to GA. Any value above the cutoff value for RGC-32, FasL, SIRT1, p-SIRT1 or below that for IL-21 or JNK1 p54 was given a -1 value, indicating clinical stability or response to GA. An MSDA score above +1 indicated a relapse or lack of response to treatment. An MSDA score below -1 indicated clinical stability or response to treatment. Our results showed that the MSDA scores generated using either four or six biomarkers had a higher sensitivity and specificity and significantly correlated with the expanded disability status scale. Although these results suggest that the MSDA test can be useful for monitoring therapeutic response to biologic agents and assessing clinically challenging situations, the present findings need to be confirmed in larger studies.

## Linked entities

- **Genes:** RGCC (regulator of cell cycle) [NCBI Gene 28984], FASLG (Fas ligand) [NCBI Gene 356], IL21 (interleukin 21) [NCBI Gene 59067], SIRT1 (sirtuin 1) [NCBI Gene 23411]
- **Chemicals:** glatiramer acetate (PubChem CID 3081884)
- **Diseases:** multiple sclerosis (MONDO:0005301), relapsing-remitting multiple sclerosis (MONDO:0005314)

## Full-text entities

- **Genes:** MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, RGCC (regulator of cell cycle) [NCBI Gene 28984] {aka C13orf15, RGC-32, RGC32, bA157L14.2}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, IL21 (interleukin 21) [NCBI Gene 59067] {aka CVID11, IL-21, Za11}, FASLG (Fas ligand) [NCBI Gene 356] {aka ALPS1B, APT1LG1, APTL, CD178, CD95-L, CD95L}
- **Diseases:** RRMS (MESH:D020529), MS (MESH:D009103)
- **Chemicals:** GA (MESH:D000068717)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11236682/full.md

## References

41 references — full list in the complete paper: https://tomesphere.com/paper/PMC11236682/full.md

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Source: https://tomesphere.com/paper/PMC11236682