Flow Cytometry Tool Could Improve Treatment Monitoring in MS

A team of researchers from New Zealand has unveiled a groundbreaking tool that they say could help personalize treatment for patients with multiple sclerosis (MS).¹

Published in Cytometry Part A, the study introduces the first comprehensive 24-parameter spectral flow cytometry panel designed to monitor how immune receptors, key drug targets in MS, vary across patients and over the course of therapy. The innovation promises to bring precision medicine closer to reality for MS, an autoimmune disease affecting over 2.8 million people worldwide.

Although more than 16 disease-modifying therapies (DMTs) are now approved, response to treatment remains unpredictable. Each DMT works by targeting specific receptors on immune cells. For instance, fingolimod (Gilenya, Tascenso; Novartis) binds to the sphingosine-1-phosphate receptor (S1PR) to trap T cells in lymph nodes, while natalizumab (Tysabri, Tyruko; Biogen) targets VLA-4 (CD49d) to prevent immune cells from entering the brain. But until now, there was no way to easily track these receptors in real time or assess whether baseline expression could predict therapeutic success.

The focus on monitoring treatment-targeted receptors follows data showing that patients with progressive MS had notable sensitivity to clozapine, the commonly used atypical antipsychotic, which increased side effects and subsequently caused patients to withdraw from the phase 1 CRISP trial.² Follow-up showed that the increased sensitivity resulted from changes in expression of dopamine and serotonin receptors, suggesting a link between changes in receptor expression levels and side effects.

Exploring this, the Wellington team developed the 24-parameter immunophenotyping panel that can simultaneously detect 12 treatment-associated receptors on major MS-relevant immune cell types—T cells, B cells, and monocytes—from a single blood sample. Using advanced spectral flow cytometry, the tool measures expression levels of key receptors like S1PR1, S1PR4, CD49d, CD20, CD52, CD80, and CD86, among others.

When tested on blood from 12 treatment-naïve patients with MS and 13 healthy controls, the panel revealed high inter-individual variability in receptor expression. Some patients showed elevated CD49d, suggesting they may benefit more from natalizumab, while others displayed higher CD80/CD86 activation markers, implying stronger response potential to drugs like dimethyl fumarate (Tecfidera; Biogen).

The study also tracked receptor changes over time in patients treated with CD20-targeting antibody ocrelizumab (Ocrevus; Genentech) and natalizumab. Those with higher baseline CD20 expression showed greater B-cell depletion and stronger therapeutic response after 12 months, while patients with low CD20 levels experienced only partial reduction. Similarly, natalizumab-treated patients with high CD49d expression saw pronounced receptor downregulation, consistent with the drug’s mode of action.

“These differences in expression profiles of some treatment-associated receptors within MS participants in relation to the mode of action of treatments highlight the potential to personalize treatments based on individual receptor expression,” explained the researchers.

Beyond research, the team envisions their single-tube, 1-hour staining protocol being adopted in clinical labs. The minimally invasive approach requires just 10 mL of blood and can be processed within 75 minutes, making it feasible for routine monitoring.

The authors caution that larger studies are needed to confirm predictive value but see strong potential for precision-guided MS care. Future work will explore how receptor patterns correlate with side effects, disease progression, and long-term outcomes.

References:

1. Robichon K, Taylor J, Milner I, Hally KE, La Flamme AC. Monitoring treatment-associated receptor expression in multiple sclerosis using a newly developed panel for spectral flow cytometry. Cytometry A. Published online September 23, 2025. doi:10.1002/cyto.a.24963

2. Flamme ACL, Abernethy D, Sim D, et al. Safety and acceptability of clozapine and risperidone in progressive multiple sclerosis: a phase I, randomised, blinded, placebo-controlled trial. BMJ Neurol Open. 2020;2(1):e000060. doi:10.1136/bmjno-2020-000060.