Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing‐remitting multiple sclerosis

Abstract

Cerebrospinal fluid (CSF) biomarkers can reflect different aspects of the pathophysiology of relapsing-remitting multiple sclerosis (RRMS). Understanding the impact of different disease modifying therapies on the CSF biomarker profile may increase their implementation in clinical practice and their appropriateness for monitoring treatment efficacy. This study investigated the influence of first-line (interferon beta) and second-line (natalizumab) therapies on seven CSF biomarkers in RRMS and their correlation with clinical and radiological outcomes. We included 59 RRMS patients and 39 healthy controls. The concentrations of C-X-C motif chemokine 13 (CXCL13), C-C motif chemokine ligand 2 (CCL2), chitinase-3-like protein 1 (CHI3L1), glial fibrillary acidic protein, neurofilament light protein (NFL), and neurogranin were determined by ELISA, and chitotriosidase (CHIT1) was analyzed by spectrofluorometry. RRMS patients had higher levels of NFL, CXCL13, CHI3L1, and CHIT1 than controls (p < 0.001). Subgroup analysis revealed higher NFL, CXCL13 and CHIT1 levels in patients treated with first-line therapy compared to second-line therapy (p = 0.008, p = 0.001 and p = 0.026, respectively). NFL and CHIT1 levels correlated with relapse status, and NFL and CXCL13 levels correlated with the formation of new magnetic resonance imaging lesions. Furthermore, we found an association between inflammatory and degenerative biomarkers. The results indicate that CSF levels of NFL, CXCL13, CHI3L1, and CHIT1 correlate with the clinical and/or radiological disease activity, providing additional dimensions in the assessment of treatment efficacy.

Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis

“…In CIS/RRMS patients, the decrease in sNfL levels correlated inversely with longer time since start of DMTs independent of recent relapses. Notably, treatment effects on CSF NfL levels have already been shown for fingolimod, natalizumab, and rituximab in MS patients 13, 14, 15, 16, 17, 47. Although this study was not primarily designed to investigate treatment effects, our results suggest that DMTs reduce sNfL levels, supporting their value for monitoring treatment response.…”

CHIT1 at Diagnosis Reflects Long‐Term Multiple Sclerosis Disease Activity

“…11,52 Only 1 previous study considered CHIT1 in the context of prognosis in MS but was limited in terms of a smaller study population and of sampling patients with an indication to switch therapies at different time points in disease instead of newly diagnosed patients. 53 Baseline (diagnostic stage) CSF CHI3L1 levels have been associated with earlier progression to disability. 50,51 There is a similar trend in our study, but we demonstrated this to be secondary to the substantially stronger association with CHIT1.…”

The role of chemokines and chemokine receptors in multiple sclerosis

“…(http://guidetopharmacology.org/GRAC/ ObjectDisplayForward?objectId = 59 (accessed 19 September 2019)) CCL2 levels in CNS are reduced during increased disease activity in MS [82]. According to the discovery of Franciotta D et al, CCL2 can be constitutively produced in the brain and CCL2 CSF levels in acute MS are lower than those in stable MS [34].…”

“…Thus, CXCL13 may be involved in recruiting mononuclear cells expressing CXCR5 or CXCR3 to the intrathecal compartment in MS [105]. CXCL13 levels are reduced by natalizumab treatment in MS [53,82]. According to Quinn JL et al, the antibody against CXCL13 could block Tfh transport and significantly reduce disease expression in Th17 EAE (EAE that induced by the myelin-specific Th17 cells transfer in C57BL / 6 J mice) [91].…”