title: Dysregulation of MS risk genes and pathways at distinct stages of disease.
abstract: OBJECTIVE
  To perform systematic transcriptomic analysis of multiple sclerosis (MS) risk genes in peripheral blood mononuclear cells (PBMCs) of subjects with distinct MS stages and describe the pathways characterized by dysregulated gene expressions.
  
  
  METHODS
  We monitored gene expression levels in PBMCs from 3 independent cohorts for a total of 297 cases (including clinically isolated syndromes (CIS), relapsing-remitting MS, primary and secondary progressive MS) and 96 healthy controls by distinct microarray platforms and quantitative PCR. Differential expression and pathway analyses for distinct MS stages were defined and validated by literature mining.
  
  
  RESULTS
  Genes located in the vicinity of MS risk variants displayed altered expression in peripheral blood at distinct stages of MS compared with the healthy population. The frequency of dysregulation was significantly higher than expected in CIS and progressive forms of MS. Pathway analysis for each MS stage-specific gene list showed that dysregulated genes contributed to pathogenic processes with scientific evidence in MS.
  
  
  CONCLUSIONS
  Systematic gene expression analysis in PBMCs highlighted selective dysregulation of MS susceptibility genes playing a role in novel and well-known pathogenic pathways.
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Sundararajan
authors.initials: S
authors.lastname: Srinivasan
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Di Dario
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Russo
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Ramesh
authors.initials: R
authors.lastname: Menon
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Brini
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Romeo
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sangalli
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Gloria Dalla
authors.initials: GD
authors.lastname: Costa
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Mariaemma
authors.initials: M
authors.lastname: Rodegher
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Radaelli
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Moiola
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cantarella
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Gianvito
authors.initials: G
authors.lastname: Martino
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Furlan
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Comi
authors.affiliation: Institute of Experimental Neurology (INSpe) (S.S., M.D.D., A.R., R.M., E.B., M. Romeo, F.S., G.D.C., M. Rodegher, M. Radaelli, L.M., G.M., R.F., V.M., G.C., C.F.), Division of Neuroscience, San Raffaele Scientific Institute, Milan; University Vita-Salute San Raffaele (S.S., E.B., G.C.), Milan; and Laboratory of Functional Genomics (D.C., E.M.), Institute for Cancer Research and Treatment (IRCC), University of Turin Medical School, Candiolo, Italy.
authors.forename: Cinthia
authors.initials: C
authors.lastname: Farina