W10 - Intrathecal CD8+CD20+ T Cells in Primary Progressive Multiple Sclerosis

Despite accumulating evidence of intrathecal inflammation in patients with primary progressive multiple sclerosis (PPMS), most anti-inflammatory therapies to treat PPMS have failed. With this study, we investigated the involvement of CD20⁺ T cells in the pathogenesis of PPMS and their involvement in the failure of the disease-modifying therapy treatment dimetyl fumarate.

Assessing CD20⁺ T cells in the blood and cerebrospinal fluid (CSF) of patients with PPMS and controls showed an increased percent of CD20⁺ T cells in blood of untreated patients, and a strong enrichment in the CSF. We also found a positive correlation between intrathecal CD8⁺CD20⁺ T cells and concentrations of myelin basic protein in the CSF and white matter brain lesion volume, and a negative correlation with thalamus volume.

Recently, we performed a randomized controlled trial investigating dimethyl fumarate treatment in patients with PPMS. Unfortunately, we found no improvement in neurodegeneration or demyelination after 48 weeks of treatment. In this study, we show that despite a decrease in intrathecal T cells following dimethyl fumarate treatment, the CD8⁺CD20⁺ T cell population was unaffected by the treatment.

In conclusion, this study shows an association between intrathecal CD8⁺CD20⁺ T cells and myelin injury as well as neurodegeneration in the CNS of patients with PPMS. Furthermore, it suggests that failure to suppress intrathecal CD8⁺CD20⁺ T cells may contribute to the lack of efficacy of treatment with dimethyl fumarate in PPMS. We conclude that CD8⁺CD20⁺ T cells likely play a role in the pathogenesis of PPMS.