# Dynamic relationship between cerebrospinal fluid immune cells and tissue damage markers in multiple sclerosis

## TL;DR

This study explores how immune cells in cerebrospinal fluid relate to tissue damage in multiple sclerosis, finding distinct immune signatures linked to disease activity.

## Contribution

The study identifies disease activity-dependent associations between specific immune cell populations and neurodegeneration markers in multiple sclerosis.

## Key findings

- RRMS patients have elevated CSF CD3+ T and CD19+ B cells compared to controls.
- Naive CD4+ T cells strongly associate with neurofilament light chain during active relapse.
- Age-related monocyte subset shifts are observed in multiple sclerosis patients.

## Abstract

Multiple sclerosis (MS) is characterized by immune-mediated demyelination and neurodegeneration. While cerebrospinal fluid (CSF) biomarkers can track tissue damage, the relationship between immune cell populations and tissue damage markers remains poorly understood. We performed comprehensive immunophenotyping of CSF samples from 63 participants [29 relapsing-remitting multiple sclerosis (RRMS), 7 primary progressive multiple sclerosis (PPMS), 27 patients with other suspected neurological diseases (OND)]. CSF levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) were measured using single-molecule array technology. Relationships between immune cell populations and biomarkers were assessed using partial correlation and multiple regression analyses, adjusting for age and sex. RRMS patients exhibited expanded lymphocyte populations compared with OND, with elevated CD3+ T cells (+5062 cells/mL, P < 0.0001) and CD19+ B cells (+180 cells/mL, P < 0.0001). Patients with multiple sclerosis showed an age-related shift in monocyte subsets, marked by increased CD14+CD16+ cells [rSP = 0.670, (95% CI: 0.44–0.81), P = 0.0029]. During active relapse, naive CD4+ T cells demonstrated the strongest association with NfL [cumulative geometric mean ratio = 2.892 (95% CI: 1.352–6.188), P < 0.0001], contrasting with non-relapse states [GMR = 0.689 (95% CI: 0.449–1.057), P = 0.101]. This study identifies distinct immunological signatures in multiple sclerosis and demonstrates disease activity-dependent associations between specific immune cell populations and tissue damage markers. The relationship between classical monocytes and GFAP in controls suggests a previously unrecognized role for myeloid cells in physiological CNS homeostasis.

Zaic et al. report that relapsing-remitting multiple sclerosis patients show elevated cerebrospinal fluid T and B lymphocytes compared with controls, with age-related monocyte subset shifts. Disease activity-dependent associations between immune cell populations and neurodegeneration markers suggest distinct immunological signatures contribute to tissue damage across different multiple sclerosis activity states.

Graphical Abstract