Cerebrospinal fluid and serum cytokine and CXCL13 profiles in clinically isolated syndrome.

Background

Clinically isolated syndrome (CIS) represents the earliest clinical manifestation of a demyelinating process suggestive of multiple sclerosis (MS). Characterization of inflammatory processes at this stage may provide additional insight into early disease biology.

Objective

To compare cerebrospinal fluid (CSF) and serum concentrations of selected cytokines and CXCL13 in patients with CIS and neurological controls.

Methods

CSF and serum samples collected between 2020 and February 2026 were analysed from 84 patients presenting with CIS, defined within the diagnostic framework of the 2017 revised McDonald criteria, and 84 controls with non-inflammatory neurological conditions. Interleukin (IL)-6, IL-8, and IL-10 were measured using chemiluminescent immunoassays, while CXCL13 was determined by enzyme-linked immunosorbent assay. Between-group differences were assessed using non-parametric statistical methods.

Results

Patients with CIS had significantly higher CSF concentrations of IL-6, IL-8, and CXCL13 than controls, with the most pronounced difference observed for CXCL13. IL-8 was elevated in CSF but not in serum, whereas IL-6 differed significantly in both compartments. The nominal difference in CSF IL-10 did not remain significant after correction for multiple comparisons.

Conclusions

Distinct CSF and serum biomarker profiles were observed at the CIS stage. These findings are compatible with heterogeneous inflammatory processes involving CNS-associated and systemic components but do not establish intrathecal production of the investigated biomarkers.