title: Identification of a gene expression signature in peripheral blood of multiple sclerosis patients treated with disease-modifying therapies.
abstract: Multiple Sclerosis (MS) is an inflammatory disease with neurodegenerative alterations, ultimately progressing to neurological handicap. Therapies are effective in counteracting inflammation but not neurodegeneration. Biomarkers predicting disease course or treatment response are lacking. We investigated whether altered gene and protein expression profiles were detectable in the peripheral blood of 78 relapsing remitting MS (RR-MS) patients treated by disease-modifying therapies. A discovery/validation study on RR-MS responsive to glatiramer acetate identified 8 differentially expressed genes: ITGA2B, ITGB3, CD177, IGJ, IL5RA, MMP8, P2RY12, and S100β. A longitudinal study on glatiramer acetate, Interferon-β, or Fingolimod treated RR-MS patients confirmed that 7 out of 8 genes were downregulated with reference to the different therapies, whereas S100β was always upregulated. Thus, we identified a peripheral gene signature associated with positive response in RR-MS which may also explain drug immunomodulatory effects. The usefulness of this signature as a biomarker needs confirmation on larger series of patients.
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cordiglieri
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Baggi
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Pia
authors.initials: P
authors.lastname: Bernasconi
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Dimos
authors.initials: D
authors.lastname: Kapetis
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Faggiani
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Consonni
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Andreetta
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Frangiamore
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Confalonieri
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Antozzi
authors.affiliation: Neurology IV - Neuroimmunology and Neuromuscular Diseases Unit, Neurological Institute "Carlo Besta", Milan, Italy. Electronic address: renato.mantegazza@istituto-besta.it.
authors.forename: Renato
authors.initials: R
authors.lastname: Mantegazza
mesh_terms: D000328:Adult; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use; D020869:Gene Expression Profiling; D000068717:Glatiramer Acetate / Q000627:therapeutic use; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D016899:Interferon-beta / Q000627:therapeutic use; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D059467:Transcriptome / Q000187:drug effects*; D055815:Young Adult
chemical_list: D007155:Immunologic Factors; D000068717:Glatiramer Acetate; D016899:Interferon-beta; D000068876:Fingolimod Hydrochloride
keywords: Multiple sclerosis; Peripheral blood biomarkers; Therapy