Quantifying Peripheral Biomarkers in Multiple Sclerosis Using Reverse-Phase HPLC

Experimental data implicate dysregulated serotonin (5-HT) levels in multiple sclerosis (MS), a chronic autoimmune-mediated demyelinating disease of the CNS, characterized by neuroinflammatory, axonal degeneration, and pronounced sexual dimorphism.The effects of clinical parameters and disease-modifying-therapies (DMTs) on peripheral 5-HT concentrations, however, remain underexplored. In response, researchers aimed to quantify peripheral levels of tryptophan (Trp), 5-HT, and 5-hydroxyindoleacetic acid (5-HIAA) in patients with relapsing-remitting MS (RRMS) and to assess the effects of BMI, DMT duration, and specific DMT regimens, with these biomarkers measured using reverse-phase high-performance liquid chromatography (HPLC) with fluorescence detection. A paper based on this study was published in Frontiers in Cell Neuroscience.¹

The prevalence and incidence of MS are rising globally, with nearly three million worldwide cases; this development reflects demographic changes and improved diagnostics, as opposed to increased individual risk.^2,3 The disease takes a huge financial toll on both individuals and society. Surprisingly, the biggest financial hit comes from people being unable to work, rather than just medical bills. Medications and unpaid care from family and friends also make up a large chunk of the expenses. When the disease gets worse or advances to a more severe type, the overall costs go up significantly.⁴

In the researcher’s cross-sectional study, 226 participants were enrolled and stratified into four groups: healthy men (HM; n = 29), healthy women (HW; n = 84), men with RRMS (MMS; n = 29), and women with RRMS (WMS; n = 84). Peripheral 5-HT levels were significantly reduced in underweight WMS (BMI < 18 kg/m²; p < 0.05), WMS with DMT duration over 4 years (p < 0.01), and WMS receiving interferon beta-1a (p < 0.01) compared to HW. No significant intergroup differences in Trp or 5-HIAA were seen across all stratifications.¹

“These findings,” write the authors of the paper,¹ “reveal a novel association between reduced peripheral 5-HT and specific clinical-therapeutic factors in WMS, extending recent MS research on sex-specific vulnerabilities, serotonergic dysregulation in neuroinflammation, and psychiatric comorbidity.”

“Although our findings need to be replicated in other populations affected by MS,” the authors continue,¹ “nevertheless, this novel integration of peripheral biomarkers with clinical variables suggest a probable clinical utility: routine psychiatric and nutritional assessments in women with MS who have low BMI, prolonged disease duration (>4 years), or are receiving IFN-β1a therapy could improve quality of life by preempting neuropsychiatric complications, pending replication in diverse cohorts. These findings build on recent evidence linking serotonin dysregulation to MS progression through adenosine deaminase (ADA) inhibition, further supporting the relevance of serotonergic pathways as modifiable targets in sex-dimorphic MS management. In addition, we propose that psychiatric and clinical evaluation of women with MS, low BMI, disease duration of more than 4 years, and treatment with IFN beta-1a may improve the quality of life for patients and their families by preventing further complications.”

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References

1. Pérez-Sánchez, G.; Aguilar-Gómez, L. A.; Vela-Sancho, G. B. et al. Reduced Peripheral Serotonin Levels in Women with Multiple Sclerosis: Associations with Underweight Status, Treatment Duration, and Use of Interferon Beta 1a. Front Cell Neurosci. 2026, 20, 1752975. DOI: 10.3389/fncel.2026.1752975
2. University of California, San Francisco MS-EPIC Team; Cree, B. A.; Gourraud, P. A. et al. Long-Term Evolution of Multiple Sclerosis Disability in the Treatment Era. Ann Neurol. 2016, 80 (4), 499-510. DOI: 10.1002/ana.24747
3. Portaccio, E.; Magyari, M.; Havrdova, E. K. et al. Multiple Sclerosis: Emerging Epidemiological Trends and Redefining the Clinical Course. Lancet Reg Health Eur. 2024, 44, 100977. DOI: 10.1016/j.lanepe.2024.100977
4. Wang, L. Y.; Wang, W. F.; Hui, S. Y. et al. Emerging Epidemiological Trends of Multiple Sclerosis Among Adults Aged 20-54 years, 1990-2021, with Projections to 2035: A Systematic Analysis for the Global Burden of Disease Study 2021. Front Neurol. 2025, 16, 1616245. DOI: 10.3389/fneur.2025.1616245