Biological activity of glatiramer acetate on Treg and anti-inflammatory monocytes persists for more than 10years in responder multiple sclerosis patients

• Published in: Clinical immunology (Orlando, Fla.) Vol. 181; pp. 83 - 88
• Main Authors: Spadaro, Michela, Montarolo, Francesca, Perga, Simona, Martire, Serena, Brescia, Federica, Malucchi, Simona, Bertolotto, Antonio
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2017
• Subjects: Adult; Aged; Antigens, CD - metabolism; Antigens, Differentiation, Myelomonocytic - metabolism; Case-Control Studies; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Female; Glatiramer acetate; Glatiramer Acetate - therapeutic use; Humans; Immunosuppressive Agents - therapeutic use; Killer Cells, Natural - immunology; Lipopolysaccharide Receptors - metabolism; M2 monocytes; Middle Aged; Monocytes - immunology; Monocytes - metabolism; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Receptors, Cell Surface - metabolism; T-Lymphocytes, Regulatory - immunology; Treatment Outcome; Treg; Young Adult; RR; Multiple sclerosis; MRI; CNS; TNF; NEDA; FITC; FBS; GA; M2 monocytes; EDSS; Glatiramer acetate; IL; PMA; MS; CReSM; Treg; DMT; PBMC; mAb; TGF; APC; PE; HD; NK; Ig; DC
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2017.06.006

Glatiramer acetate (GA) is a widely used treatment for multiple sclerosis (MS), with incompletely defined mechanism of action. Short-term studies suggested its involvement in the modulation of anti-inflammatory cytokines and regulatory T cells (Treg), while long-term effect is still unknown.
To investigate this aspect, we analyzed by flow-cytometry peripheral-blood Treg, natural killer (NK), CD4 and CD8 T-cells and anti-inflammatory CD14+CD163+ monocytes from 37 healthy donor and 90 RRMS patients divided in untreated, treated with GA for 12months and from 34 to 192months.
While NK, CD4 and CD8 T-cells did not show any significant differences among groups over time, we demonstrated that GA increased the anti-inflammatory monocytes and restored the Treg level in both GA-treated groups. Both these effects are a characteristic of responder patients and are observed not just in short-term but even after as long as a decade of GA treatment.
•Treg are impaired in RRMS patients compared to controls.•GA restores the Treg percentage in RRMS patients.•GA increases the percentage of M2 cells in RRMS patients.•Modifications persist for >10years.