title: Longitudinal assessment of immuno-metabolic parameters in multiple sclerosis patients during treatment with glatiramer acetate.
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.
  
  
  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.
authors.affiliation: Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli "Federico II", Napoli, Italy.
authors.forename: Pietro B
authors.initials: PB
authors.lastname: Carrieri
authors.affiliation: 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.
authors.forename: Fortunata
authors.initials: F
authors.lastname: Carbone
authors.affiliation: Dipartimento di Medicina Clinica e Chirurgia, Università di Napoli "Federico II", Napoli, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Perna
authors.affiliation: Dipartimento di Sanità Pubblica, Università di Napoli "Federico II", Napoli, Italy.
authors.forename: Dario
authors.initials: D
authors.lastname: Bruzzese
authors.affiliation: 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.
authors.forename: Claudia
authors.initials: C
authors.lastname: La Rocca
authors.affiliation: 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.
authors.forename: Mario
authors.initials: M
authors.lastname: Galgani
authors.affiliation: Dipartimento di Neuroscienze, Scienze Riproduttive ed Odontostomatologiche, Università di Napoli "Federico II", Napoli, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Montella
authors.affiliation: 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.
authors.forename: Maria
authors.initials: M
authors.lastname: Petracca
authors.affiliation: Dipartimento di Neurologia, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Napoli, Italy.
authors.forename: Ciro
authors.initials: C
authors.lastname: Florio
authors.affiliation: Dipartimento di Neurologia, Azienda Ospedaliera di Rilievo Nazionale Cardarelli, Napoli, Italy.
authors.forename: Giorgia T
authors.initials: GT
authors.lastname: Maniscalco
authors.affiliation: Unità Operativa Complessa di Neurologia, Azienda Ospedaliera di Rilevo Nazionale S. Giuseppe Moscati, Avellino, Italy.
authors.forename: Daniele L A
authors.initials: DL
authors.lastname: Spitaleri
authors.affiliation: Dipartimento di Neuroscienze, Unità di Malattie Demielinizzanti, Azienda Ospedaliera Universitaria S. Giovanni di Dio e Ruggi d'Aragona, Salerno, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Iuliano
authors.affiliation: Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Tedeschi
authors.affiliation: Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Marida
authors.initials: M
authors.lastname: Della Corte
authors.affiliation: Dipartimento di Scienze Mediche, Chirurgiche, Neurologiche, Metaboliche e dell'Invecchiamento, Seconda Università di Napoli, Napoli, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Bonavita
authors.affiliation: 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.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Matarese
mesh_terms: D000328:Adult; D015415:Biomarkers; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D000068717:Glatiramer Acetate; D006801:Humans; D020738:Leptin / Q000097:blood; D008137:Longitudinal Studies; D018655:Lymphocyte Count; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D010455:Peptides / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D020738:Leptin; D010455:Peptides; D000068717:Glatiramer Acetate
keywords: Glatiramer acetate; Metabolism; Multiple sclerosis