What is the clinical evidence from this study?

Study design: Observational. Population: Relapsing Multiple Sclerosis (n=150). Intervention: High CSF CXCL13 concentration vs. Low CSF CXCL13 concentration. Primary outcome: Time to first relapse (HR 12.61, 95% CI 2.53-62.84, p=0.002).

October 10, 2022Molecular Neurobiology39 citationsOpen Access

CSF CXCL13 and Chitinase 3-like-1 Levels Predict Disease Course in Relapsing Multiple Sclerosis

MLMatteo LucchiniUniversità Cattolica del Sacro Cuore VAValeria De ArcangelisAgostino Gemelli University Polyclinic GPGeny PiroUniversity of Verona

Key Result

High CSF CXCL13 levels in relapsing multiple sclerosis patients significantly increased the risk of relapse (HR 12.61) compared to low levels.

Study Design

Type

Observational (n=150)

Multicenter

Structured PICO

Do CSF levels of CXCL13 and CHI3L1 predict disease course and clinical/radiological activity in patients with relapsing multiple sclerosis?

Population

150 patients including relapsing multiple sclerosis (RMS, n=107), progressive multiple sclerosis (PMS, n=18), other inflammatory neurological disorders (OIND, n=10), and other non-inflammatory neurological disorders (ONIND, n=15)

Intervention

Measurement of CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13

Comparator

Comparison between MS subtypes (RMS vs PMS) and control groups (OIND, ONIND)

Outcome

Clinical and radiological activity (relapse, MRI activity, any evidence of disease activity, conversion to clinically defined MS)surrogate

High CSF levels of CXCL13 and CHI3L1 are strong prognostic biomarkers for predicting relapse and MRI activity in patients with relapsing multiple sclerosis.

Main Result

Effect estimate: HR 12.61 (95% CI 2.53-62.84)

p-value: p=0.002

Limitations

Few patients remained untreated or were directly exposed to highly effective disease-modifying therapies, potentially confounding clinical and radiological outcomes.
Different sizes of the study groups, with RMS patients representing nearly 70% of the whole population.

Abstract

Several biomarkers from multiple sclerosis (MS) patients' biological fluids have been considered to support diagnosis, predict disease course, and evaluate treatment response. In this study, we assessed the CSF concentration of selected molecules implicated in the MS pathological process. To investigate the diagnostic and prognostic significance of CSF concentration of target candidate biomarkers in both relapsing (RMS, n = 107) and progressive (PMS, n = 18) MS patients and in other inflammatory (OIND, n = 10) and non-inflammatory (ONIND, n = 15) neurological disorders. We measured the CSF concentration of APRIL, BAFF, CHI3L1, CCL-2, CXCL-8, CXCL-10, CXCL-12, CXCL-13 through a Luminex Assay. MS patients were prospectively evaluated, and clinical and radiological activity were recorded. CHI3L1 and CXCL13 CSF levels were significantly higher in both MS groups compared to control groups, while CCL2, BAFF, and APRIL concentrations were lower in RMS patients compared to PMS and OIND. Considering RMS patients with a single demyelinating event, higher concentrations of CHI3L1, CXCL10, CXCL12, and CXCL13 were recorded in patients who converted to clinically defined MS(CDMS). RMS patients in the CXCL13 and CHI3L1 high concentration group had a significantly higher risk of relapse (HR 12.61 and 4.57), MRI activity (HR 7.04 and 2.46), and of any evidence of disease activity (HR 12.13 and 2.90) during follow-up. CSF CXCL13 and CHI3L1 levels represent very good prognostic biomarkers in RMS patients, and therefore can be helpful in the treatment choice. Higher CSF concentrations of neuro-inflammatory biomarkers were associated with a higher risk of conversion to CDMS in patients with a first clinical demyelinating event. Differential CSF BAFF and APRIL levels between RMS and PMS suggest a different modulation of B-cells pathways in the different phases of the disease.

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