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.

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

Ziliotto, Nicole
Primo
;
Bernardi, Francesco
Secondo
;
Baroni, Marcello;Zamboni, Paolo;Marchetti, Giovanna;
2018

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.
2018
Ziliotto, Nicole; Bernardi, Francesco; Jakimovski, Dejan; Baroni, Marcello; Bergsland, Niels; Ramasamy, Deepa P.; Weinstock-Guttman, Bianca; Zamboni, Paolo; Marchetti, Giovanna; Zivadinov, Robert; Ramanathan, Murali
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