Pietro B Carrieri1, Fortunata Carbone2, Francesco Perna3, Dario Bruzzese4, Claudia La Rocca2, Mario Galgani2, Silvana Montella1, Maria Petracca5, Ciro Florio6, Giorgia T Maniscalco6, Daniele L A Spitaleri7, Gerardo Iuliano8, Gioacchino Tedeschi9, Marida Della Corte9, Simona Bonavita9, Giuseppe Matarese10. 1. Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli "Federico II", Napoli, Italy. 2. Laboratorio di Immunologia, Istituto di Endocrinologia e Oncologia Sperimentale, Consiglio Nazionale delle Ricerche (IEOS-CNR), c/o Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli "Federico II", Napoli, Italy. 3. Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli "Federico II", Napoli, Italy. 4. Dipartimento di Sanità Pubblica, Università di Napoli "Federico II", Napoli, Italy. 5. Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli "Federico II", Napoli, Italy; Department of Neurology, Icahn School of Medicine at Mount Sinai, NY, USA. 6. Dipartimento di Neurologia, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Napoli, Italy. 7. Unità Operativa Complessa di Neurologia, Azienda Ospedaliera di Rilevo Nazionale S. Giuseppe Moscati, Avellino, Italy. 8. Dipartimento di Neuroscienze, Unità di Malattie Demielinizzanti, Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy. 9. Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, Seconda Università di Napoli, Napoli, Italy. 10. Dipartimento di Medicina e Chirurgia, Facoltà di Medicina e Chirurgia, Università di Salerno, Baronissi Campus, Baronissi, Salerno, Italy; IRCCS MultiMedica, Milano, Italy. Electronic address: gmatarese@unisa.it.
Abstract
OBJECTIVE: We investigated the effect of glatiramer acetate (GA) on the modulation of immune cell subpopulations and serum levels of multiple immune/metabolic markers in patients with relapsing-remitting multiple sclerosis (RRMS) to understand whether the treatment with GA could induce a specific change in the immunometabolic asset of patients with RRMS. MATERIAL AND METHODS: We performed an extensive peripheral blood immunophenotyping and measured serum levels of several parameters involved in the pathogenesis of RRMS and also relevant in the pathogenesis of metabolic syndrome and obesity such as leptin, soluble leptin-receptor (sLep-R), myeloperoxidase (MPO), soluble CD40 ligand (sCD40-L), soluble tumor necrosis factor-receptor (sTNF-R), monocyte chemoattractant protein 1 (MCP-1), soluble Inter-Cellular Adhesion Molecule-1 (sICAM-1) and osteoprotegerin (OPG), in 20 naïve-to-treatment RRMS patients and 20 healthy controls. We repeated these analyses over time at 6 and 12 months after starting GA treatment. RESULTS: Our analysis showed that naïve-to-treatment RRMS patients had a lower number of CD16(+)CD56(+) NK cells, CD19(+) B cells, CD4(+) T cells co-expressing the MHC class II activation marker HLA-DR (CD4(+)DR(+)) and naïve CD4(+)CD45RA(+) T cells in basal conditions. GA treatment induced a specific and significant decrease of circulating CD19(+) B cells. Naïve-to-treatment RRMS patients also showed a significantly higher number of CD4(+) T cells with a memory phenotype (CD4(+)CD45RO(+)) whose peripheral frequency was not affected by GA treatment. These changes over time associated with a higher serum concentration of leptin and lower levels of MPO. GA treatment also reduced significantly the circulating levels of sCD40-L and sTNF-R overtime. CONCLUSIONS: Our data suggest that the clinical outcome of GA treatment is associated with changes in immune cell subpopulations and modulation of specific immunometabolic markers. These data add substantial evidence of the immune modulating effect of GA during RRMS and could be of relevance in understanding the pathogenesis of disease and its follow-up.
OBJECTIVE: We investigated the effect of glatiramer acetate (GA) on the modulation of immune cell subpopulations and serum levels of multiple immune/metabolic markers in patients with relapsing-remitting multiple sclerosis (RRMS) to understand whether the treatment with GA could induce a specific change in the immunometabolic asset of patients with RRMS. MATERIAL AND METHODS: We performed an extensive peripheral blood immunophenotyping and measured serum levels of several parameters involved in the pathogenesis of RRMS and also relevant in the pathogenesis of metabolic syndrome and obesity such as leptin, soluble leptin-receptor (sLep-R), myeloperoxidase (MPO), soluble CD40 ligand (sCD40-L), soluble tumor necrosis factor-receptor (sTNF-R), monocyte chemoattractant protein 1 (MCP-1), soluble Inter-Cellular Adhesion Molecule-1 (sICAM-1) and osteoprotegerin (OPG), in 20 naïve-to-treatment RRMS patients and 20 healthy controls. We repeated these analyses over time at 6 and 12 months after starting GA treatment. RESULTS: Our analysis showed that naïve-to-treatment RRMS patients had a lower number of CD16(+)CD56(+) NK cells, CD19(+) B cells, CD4(+) T cells co-expressing the MHC class II activation marker HLA-DR (CD4(+)DR(+)) and naïve CD4(+)CD45RA(+) T cells in basal conditions. GA treatment induced a specific and significant decrease of circulating CD19(+) B cells. Naïve-to-treatment RRMS patients also showed a significantly higher number of CD4(+) T cells with a memory phenotype (CD4(+)CD45RO(+)) whose peripheral frequency was not affected by GA treatment. These changes over time associated with a higher serum concentration of leptin and lower levels of MPO. GA treatment also reduced significantly the circulating levels of sCD40-L and sTNF-R overtime. CONCLUSIONS: Our data suggest that the clinical outcome of GA treatment is associated with changes in immune cell subpopulations and modulation of specific immunometabolic markers. These data add substantial evidence of the immune modulating effect of GA during RRMS and could be of relevance in understanding the pathogenesis of disease and its follow-up.
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