Abstract Details

In MS, elevated levels of T cells and auto-antibodies targeting myelin/neuronal antigens are present within the cerebrospinal fluid (CSF). While different immune cell subsets contribute to MS pathogenesis, T and B lymphocytes remain the primary targets of immune-based therapies. Following axonal injury, neurofilament light chain (NfL) can be measured in CSF and plasma, and is a potential  biomarker of immune-mediated damage. 

To determine whether levels and/or ratios of MS disease-relevant immune cells in the CSF and plasma are associated with NfL levels, and how they are impacted by disease-modifying treatments (DMTs). 

CSF and blood were obtained from relapsing-remitting (RRMS) patients. Both bodily fluids were processed to isolate immune cells (CSF) and peripheral blood mononuclear cells (PBMCs; blood); plasma was also collected and all samples were cryopreserved. Control samples were collected from participants with other neurological conditions, in addition to RRMS patients prescribed moderate or high-efficacy DMTs. Flow cytometry of immune cells were performed, and both CSF and plasma NfL were measured by ELISA or SiMoA. 

Treatment naive RRMS patients had significant increases in the numbers of CD3+CD8+ T cells and CD19+ B cells in CSF compared to controls. DMT-treated RRMS patients had significantly lower numbers of CD45+ leukocytes, CD4+ T cells, CD19+ B cells and CD16+CD56+ NK cells. In RRMS, CSF NfL levels were positively correlated with CSF B cells and NK cells while IgG index levels were positively correlated with CSF NfL and all immune cell subsets measured, including memory T and B cells. 

Our study demonstrates that T and B cell numbers are significantly increased in CSF obtained from RRMS patients and correlates with NfL and IgG index levels. With DMTs, numbers of immune cells and NfL return to levels similar to non-inflammatory controls. Our results suggest inflammatory measures of DMT responsiveness can be measured within the CSF.