Increased CCL18 plasma levels are associated with neurodegenerative MRI outcomes in multiple sclerosis patients

Abstract

Background: Chemokine ligands and co-stimulatory factors are involved in macrophage activation and differentiation processes that could contribute to multiple sclerosis (MS) pathogenesis.

Objective: To investigate associations of C-C motif Ligand 18 (CCL18), C-C motif ligand 5 (CCL5) and soluble Cluster of Differentiation 86 (sCD86) with clinical and MRI measures in MS patients.

Methods: Plasma levels of CCL18, CCL5 and sCD86 were evaluated in 138 MS patients (85 relapsing-remitting, RR-MS; 53 progressive, P-MS), and in 42 age- and sex-matched healthy individuals (HI). All subjects underwent standardized 3T MRI and clinical examinations. Multiple regression analysis of MRI outcomes as dependent variables was performed with age, gender, having P-MS, and plasma proteins as predictor variables.

Results: Higher CCL18 plasma levels were found in P-MS (median = 51.5, IQR = 41.0-63.6 ng/mL) compared to RR-MS (median = 43.0, IQR = 29.1-55.0 ng/mL, p = 0.014) and to HI (median = 41.3, IQR = 30.9-54.1 ng/mL, p = 0.009). Disease-modifying treatments altered CCL5 (p = 0.036) and sCD86 (p < 0.001) levels. Higher CCL18 levels were associated with increased lateral ventricular volume (p = 0.006) and T2 lesion volume (LV) (p = 0.034), and decreased grey matter (p = 0.006), thalamic (p = 0.007) and cortical (p = 0.01) volumes.

Conclusions: Our results provide evidence that higher CCL18 plasma levels are associated with more severe inflammatory and neurodegenerative brain MRI outcomes in MS.

Keywords: CCL18; CCL5; CD86; MRI; Multiple sclerosis; Neurodegeneration.