The field of multiple sclerosis (MS) has seen a tremendous expansion of treatments in the past decade, yet the only measure of treatment response is waiting for breakthrough disease activity to occur. There is a need to develop biomarkers that can stratify the risk of impeding disease activity to enable personalized and mechanistically-guided treatment decision making in MS. Our recent work demonstrated that the immunomodulatory mechanism of dimethyl-fumarate (DMF) is the reduction of brain-homing CCR6+ T-cells via modulation of DNA methylation at specific genomic loci. Would the presence or absence of this mechanistic response stratify the risk of impeding disease activity in patients treated with DMF?

Logistic regression revealed that, among various clinical and immunophenotypic metrics, the percentage of brain-homing CCR6+ T-cells at the time of enrollment was a highly significant predictor of breakthrough disease activity over the subsequent 20 months. DMF-treated patients with the highest percentage of those cells (absence of mechanistic response) had a significantly higher risk of disease activity compared to patients with a low percentage (presence of mechanistic response). Interestingly, these high-risk patients had a similar percentage of CCR6+ T-cells as untreated MS patients.

These results suggest that changes in brain-homing CCR6+ cells in the periphery could precede disease activity by many months and thus serve as a biomarker of treatment response at least for DMF therapy. It is unknown however if this could be applied to the other disease modifying therapies in MS.