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

• Published in: Frontiers in immunology Vol. 15; p. 1338585
• Main Authors: Tatomir, Alexandru, Anselmo, Freidrich, Boodhoo, Dallas, Chen, Hegang, Mekala, Armugam P, Nguyen, Vinh, Cuevas, Jacob, Rus, Violeta, Rus, Horea
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27-06-2024
• Subjects: Adult; Biomarkers; Fas Ligand Protein - metabolism; Female; Glatiramer Acetate - therapeutic use; Humans; Immunology; Immunosuppressive Agents - therapeutic use; Interleukins; JNK1; Male; Middle Aged; Mitogen-Activated Protein Kinase 8 - metabolism; multiple sclerosis; Multiple Sclerosis - diagnosis; Multiple Sclerosis - drug therapy; Multiple Sclerosis, Relapsing-Remitting - diagnosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; peripheral blood mononuclear cells; Pilot Projects; RGC-32; Severity of Illness Index; SIRT1; Sirtuin 1 - metabolism; Treatment Outcome; peripheral blood mononuclear cells; biomarkers; multiple sclerosis; JNK1; RGC-32; glatiramer acetate; SIRT1
• DOI: 10.3389/fimmu.2024.1338585
• EISSN: 1664-3224

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.