title: Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis.
abstract: Understanding the mechanisms that sustain the effects of disease modifying drugs in multiple sclerosis (MS) may help refine current therapies and improve our knowledge of disease pathogenesis. By using cDNA microarrays, we investigated gene expression in the peripheral blood mononuclear cells (PBMC) of 7 MS patients, at baseline (T0) as well as after 1 (T1) and 3 months (T3) of interferon beta-1a (IFN-beta-1a; Rebif 44 microg) therapy. Gene expression changes involved genes of both immunological and non-immunological significance. We validated IL-10 up-regulation, which is in accordance with previous reports, and other novel changes that underscore the capacity of IFN-beta to impair antigen presentation and migration of inflammatory elements into the central nervous system (up-regulation of filamin B and down-regulation of IL-16 and rab7). Overall, gene expression changes became less pronounced after 3 months of therapy, suggesting a homeostatic response to IFN-beta. This may be of use for the design of new treatment schedules.
authors.affiliation: Department of Neurology and Center for Experimental Neurological Therapy, S Andrea Hospital, University of Rome La Sapienza, Rome, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Annibali
authors.forename: Simone
authors.initials: S
authors.lastname: Di Giovanni
authors.forename: Stefania
authors.initials: S
authors.lastname: Cannoni
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Giugni
authors.forename: Roberto
authors.initials: R
authors.lastname: Bomprezzi
authors.forename: Carlo
authors.initials: C
authors.lastname: Mattei
authors.forename: Abdel
authors.initials: A
authors.lastname: Elkahloun
authors.forename: Eliana Marina
authors.initials: EM
authors.lastname: Coccia
authors.forename: Marco
authors.initials: M
authors.lastname: Alfò
authors.forename: Francesco
authors.initials: F
authors.lastname: Orzi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ristori
authors.forename: Marco
authors.initials: M
authors.lastname: Salvetti
mesh_terms: D000328:Adult; D003285:Contractile Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D005260:Female; D064448:Filamins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D019410:Interleukin-16 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008840:Microfilament Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020691:rab GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D000090802:rab7 GTP-Binding Proteins
chemical_list: D003285:Contractile Proteins; D064448:Filamins; D019410:Interleukin-16; D008840:Microfilament Proteins; D000090802:rab7 GTP-Binding Proteins; C000716463:rab7 GTP-binding proteins, human; D016753:Interleukin-10; D016899:Interferon-beta; D020691:rab GTP-Binding Proteins; D000068556:Interferon beta-1a