ID: 144. Issue 1 (November 2015)

• Record Type: Journal Article
• Authors: Harari, Daniel; Orr, Irit; Rotkopf, Ron; Baranzini, Sergio; Schreiber, Gideon
• Is Part Of: Cytokine. Volume 76:Issue 1(2015)
• Page Start: 93
• Publication Date: 2015-11
• Subjects: Cytokines -- Periodicals; 571.844
• DOI: 10.1016/j.cyto.2015.08.171
• Languages: English
• ISSNs: 1043-4666

Abstract

<abstract xml:lang="en" abstract-type="author" id="ab005"> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p id="sp005">We analysed gene expression microarray data from whole blood samples from 228 multiple sclerosis (MS) patients either untreated or treated with one of three alternative commonly used interferon beta (IFN<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7pxq" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si1.gif" display="inline" overflow="scroll" id="d13e108" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi mathvariant="normal">β</mml:mi><mml:mo stretchy="false">)</mml:mo></mml:mrow></mml:math></alternatives></inline-formula> disease modifying drugs: Avonex® (<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7r2z" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e115" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mo>×</mml:mo></mml:mrow></mml:math></alternatives></inline-formula>1 weekly), Betaseron® (every second day) or Rebif® (<inline-formula><alternatives><inline-graphic xlink:href="ark:/27927/pgj2n6x7r2z" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /><mml:math altimg="si2.gif" display="inline" overflow="scroll" id="d13e120" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mo>×</mml:mo></mml:mrow></mml:math></alternatives></inline-formula>3 weekly). Patient injections were not timed to coordinate with sample collections, thus providing a global transcriptomic profile for each population of patients studied. Three hundred and fifty-one genes were significantly differentially expressed by at least one of the IFNβ drugs. Despite the different drug sources with distinct injection and dosage protocols, a striking similarity was found in the identity and functional classes of the differentially expressed genes induced. Using the 25 most-upregulated genes, we defined a robust IFNβ gene expression signature that quantifies the IFN activation state per blood sample collected irrespective of the type of IFNβ therapy. This 25-gene signature also defined basal IFN activation states among untreated MS patients, which differed among individuals but remained relatively constant per patient with time. The maximum drug-induced IFN-activation state was similar for all three drugs despite a 1.7–2.0-fold diminished average effect for Avonex. This and a more erratic effect of Avonex per patient across longitudinal measurements is likely a result of its reduced injection frequency. In summary, we have defined a robust blood-derived type I IFN gene signature from MS patients. This signature could potentially serve to generically quantify the systemic Type I IFN activation status for any other clinical manifestation, inclusive of other autoimmune diseases.</p> </sec> </abstract>