Pre-treatment T-cell subsets associate with fingolimod treatment responsiveness in multiple sclerosis

Biomarkers predicting fingolimod (FTY) treatment response in relapsing-remitting multiple sclerosis (RRMS) are lacking. Here, we performed extensive functional immunophenotyping using multiparametric flow cytometry to examine peripheral immune changes under FTY treatment and explore biomarkers of FTY treatment response. From among 135 RRMS patients who initiated FTY in a 2-year multicentre observational study, 36 were classified as 'Active' or 'Stable' based on clinical and/or radiological activity on-treatment. Flow cytometric analysis of immune cell subsets was performed on pre- and on-treatment peripheral blood mononuclear cells (PBMC) samples. Decreased absolute counts of B cells and most T-cell subsets were seen on-treatment. Senescent CD8 + T cells, CD56 + T cells, CD56^dim natural killer cells, monocytes and dendritic cells were not reduced in number and hence relatively increased in frequency on-treatment. An unbiased multiparametric and traditional manual analysis of T-cell subsets suggested a higher pre-treatment frequency of CD4 + central memory T cells (TCM) in patients who were subsequently Active versus Stable on-treatment. Lower pre-treatment terminally differentiated effector memory (TEMRA) cell frequencies were also seen in the subsequently Active cohort. Together, our data highlight differential effects of FTY on peripheral immune cell subsets and suggest that pre-treatment T-cell subset frequencies may have value in predicting FTY treatment response.