Monitoring Treatment‐Associated Receptor Expression in Multiple Sclerosis Using a Newly Developed Panel for Spectral Flow Cytometry

Multiple sclerosis (MS) is a chronic, immune-mediated autoimmune disease characterized by the infiltration of autoreactive T cells and other inflammatory immune cells from the periphery into the central nervous system. Currently, there is no cure for MS, and treatment consists of disease-modifying therapies (DMTs), most of which modify or delete specific immune cell populations. These populations express crucial MS treatment-associated receptors, which may be differentially expressed in each patient, and thus each drug may affect individuals differently. Here, we developed the first comprehensive 24-parameter flow cytometry immunophenotyping panel to evaluate treatment-associated receptor expression on the major MS-associated immune cells in whole blood. Analyzing whole blood samples from treatment-naïve individuals with MS using this panel, we demonstrated that expression levels of these receptors vary between individuals. Response to the chosen DMT treatment also differed across participants. When monitoring the receptor expression during the course of treatment, we detected an increased response to treatment when receptor expression was elevated at the start of treatment. This panel reliably detects these receptors in MS treatment-naïve participants and enables monitoring of their expression throughout treatment. This tool will enable deep interrogation of the immune receptors targeted by MS therapies and highlights that treatment-associated receptor expression levels might be used to predict or correlate with treatment response.