Genomic effects of IFN-beta in multiple sclerosis patients

• Published in: The Journal of immunology (1950) Vol. 171; no. 5; pp. 2694 - 2702
• Main Authors: Weinstock-Guttman, Bianca, Badgett, Darlene, Patrick, Kara, Hartrich, Laura, Santos, Roseane, Hall, Dennis, Baier, Monika, Feichter, Joan, Ramanathan, Murali
• Format: Journal Article
• Language: English
• Published: United States 01-09-2003
• Subjects: Adult; Antigens, CD - biosynthesis; Antigens, CD - genetics; Antigens, Differentiation, T-Lymphocyte - biosynthesis; Antigens, Differentiation, T-Lymphocyte - genetics; Antiviral Agents - biosynthesis; Antiviral Agents - genetics; Bayes Theorem; Biomarkers - analysis; Female; Gene Expression Profiling - methods; Gene Expression Profiling - statistics & numerical data; Genetic Variation - immunology; Humans; Injections, Intramuscular; Interferon-beta - administration & dosage; Interferon-beta - pharmacology; Interferon-beta - therapeutic use; Janus Kinase 1; Lectins, C-Type; Lymphocyte Activation - genetics; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting - genetics; Multiple Sclerosis, Relapsing-Remitting - immunology; Multiple Sclerosis, Relapsing-Remitting - metabolism; Polymerase Chain Reaction - methods; Polymerase Chain Reaction - statistics & numerical data; Protein Processing, Post-Translational - immunology; Protein-Tyrosine Kinases - biosynthesis; Protein-Tyrosine Kinases - genetics; RNA, Messenger - biosynthesis; Signal Transduction - genetics; Signal Transduction - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.5.2694

The purpose of this report was to characterize the dynamics of the gene expression cascades induced by an IFN-beta-1a treatment regimen in multiple sclerosis patients and to examine the molecular mechanisms potentially capable of causing heterogeneity in response to therapy. In this open-label pharmacodynamic study design, peripheral blood was obtained from eight relapsing-remitting multiple sclerosis patients just before and at 1, 2, 4, 8, 24, 48, 120, and 168 h after i.m. injection of 30 micro g of IFN-beta-1a. The total RNA was isolated from monocyte-depleted PBL and analyzed using cDNA microarrays containing probes for >4000 known genes. IFN-beta-1a treatment resulted in selective, time-dependent effects on multiple genes. The mRNAs for genes implicated in the anti-viral response, e.g., double-stranded RNA-dependent protein kinase, myxovirus resistance proteins 1 and 2, and guanylate binding proteins 1 and 2 were rapidly induced within 1-4 h of IFN-beta treatment. The mRNAs for several genes involved in IFN-beta signaling, such as IFN-alpha/beta receptor-2 and Stat1, were also increased. The mRNAs for lymphocyte activation markers, such as IFN-induced transmembrane protein 1 (9-27), IFN-induced transmembrane protein 2 (1-8D), beta(2)-microglobulin, and CD69, were also increased in a time-dependent manner. The findings demonstrate that IFN-beta treatment induces specific and time-dependent changes in multiple mRNAs in lymphocytes of multiple sclerosis patients that could provide a framework for rapid monitoring of the response to therapy.