Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis

Viviana Annibali; Simone Di Giovanni; Stefania Cannoni; Elisabetta Giugni; Roberto Bomprezzi; Carlo Mattei; Abdel Elkahloun; Eliana Marina Coccia; Marco Alfò; Francesco Orzi; Giovanni Ristori; Marco Salvetti

doi:10.1080/08916930601135241

Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis

Autoimmunity. 2007 Feb;40(1):16-22. doi: 10.1080/08916930601135241.

Authors

Viviana Annibali¹, Simone Di Giovanni, Stefania Cannoni, Elisabetta Giugni, Roberto Bomprezzi, Carlo Mattei, Abdel Elkahloun, Eliana Marina Coccia, Marco Alfò, Francesco Orzi, Giovanni Ristori, Marco Salvetti

Affiliation

¹ Department of Neurology and Center for Experimental Neurological Therapy, S Andrea Hospital, University of Rome La Sapienza, Rome, Italy.

PMID: 17364493
DOI: 10.1080/08916930601135241

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.

MeSH terms

Adult
Contractile Proteins / biosynthesis
Contractile Proteins / genetics
Contractile Proteins / immunology
Female
Filamins
Gene Expression Profiling
Gene Expression Regulation
Homeostasis
Humans
Interferon beta-1a
Interferon-beta / immunology
Interferon-beta / therapeutic use*
Interleukin-10 / biosynthesis
Interleukin-10 / genetics
Interleukin-10 / immunology
Interleukin-16 / biosynthesis
Interleukin-16 / genetics
Interleukin-16 / immunology
Magnetic Resonance Imaging / methods
Male
Microfilament Proteins / biosynthesis
Microfilament Proteins / genetics
Microfilament Proteins / immunology
Multiple Sclerosis / drug therapy*
Multiple Sclerosis / genetics*
Multiple Sclerosis / immunology
Oligonucleotide Array Sequence Analysis / methods
rab GTP-Binding Proteins / biosynthesis
rab GTP-Binding Proteins / genetics
rab GTP-Binding Proteins / immunology
rab7 GTP-Binding Proteins

Substances

Contractile Proteins
Filamins
Interleukin-16
Microfilament Proteins
rab7 GTP-Binding Proteins
rab7 GTP-binding proteins, human
Interleukin-10
Interferon-beta
rab GTP-Binding Proteins
Interferon beta-1a