# Effects of disease-modifying drugs on serum neurofilament light chain, chitinase-3-like-1 protein levels, and selected plasmacytoid dendritic cell biomarkers in relapsing-remitting multiple sclerosis

## TL;DR

This study examines how different drugs for multiple sclerosis affect specific biomarkers in the blood, finding that some drugs increase levels of these markers more than others.

## Contribution

The study compares the effects of three disease-modifying drugs on serum biomarkers in RRMS patients, revealing distinct impacts on NFL and CHI3L1 levels.

## Key findings

- Serum NFL and CHI3L1 levels were significantly higher in MS patients compared to healthy controls.
- B-cell therapy (rituximab) led to higher NFL and CHI3L1 levels compared to IFN-b-1A and fingolimod.
- DMDs did not affect the migratory and tolerogenic functions of plasmacytoid dendritic cells.

## Abstract

Multiple sclerosis (MS) is a neurodegenerative central nervous system disorder causing axonal damage and disability. Relapses develop over hours or days and then subside over weeks. Disease-modifying drugs (DMDs) influence disease activity. Interferon beta-1A (IFN-b-1A) is a widely used first-line treatment for relapsing remitting MS (RRMS) that reduces central nervous system inflammation. Fingolimod affects lymphocyte trafficking. B-cell therapy (rituximab) depletes circulating CD20+ B cells in cerebrospinal fluid, but their specific effects in RRMS remain limited.

The aim of the present study was to evaluate the effect of DMDs such as IFN-b-1A, fingolimod and rituximab on neurofilament light chain (NFL) and chitinase 3-like 1 (CHI3L1) serum levels, and some biomarkers of plasmacytoid dendritic cells (pDCs) in RRMS patients.

Thirty healthy controls and 44 RRMS patients actively receiving their DMDs, were recruited into this study. Patients were divided into three groups according to DMDs type: Group 1 (n = 17) received IFN-b-1A, Group 2 (n = 20) received fingolimod, and Group 3 (n = 7) received rituximab. Patients of all ages and both sexes were included.

Serum NFL (84.1% sensitivity and 60.0% specificity) and CHI3L1 (90.9% sensitivity and 73.0% specificity) levels were higher in patients than in controls (p ≤ 0.001), with higher levels of NFL in the B-cell therapy group compared with IFN-b-1A (p ≤ 0.001) and fingolimod (p = 0.005), and higher levels of CHI3L1 in the B-cell group compared to IFN-b-1A (p = 0.001) and fingolimod (p = 0.015). Plasmacytoid dendritic cells showed no difference in tolerogenic and migratory function between the DMDs groups.

Disease-modifying drug type (IFN-b-1A, fingolimod, and B-cell therapy) impacts NFL and CHI3L1 serum levels as drug response biomarkers and relates to clinical data of MS patients, but has no diverse impact on the migratory and tolerogenic function of pDCs.

The serum NFL and CHI3L1 need to be validated as drug response biomarkers in RRMS patients, evaluating the DMDs’ effect on immunocellular level by studying migratory and tolerogenic functions of pDCs.