Prediction of Therapeutic Responses to Tocilizumab in Patients With Rheumatoid Arthritis: Biomarkers Identified by Analysis of Gene Expression in Peripheral Blood Mononuclear Cells Using Genome‐Wide DNA Microarray. Issue 6 (June 2014)

• Record Type: Journal Article
• Authors: Sanayama, Yoshie; Ikeda, Kei; Saito, Yukari; Kagami, Shin‐ichiro; Yamagata, Mieko; Furuta, Shunsuke; Kashiwakuma, Daisuke; Iwamoto, Itsuo; Umibe, Takeshi; Nawata, Yasushi; Matsumura, Ryutaro; Sugiyama, Takao; Sueishi, Makoto; Hiraguri, Masaki; Nonaka, Ken; Ohara, Osamu; Nakajima, Hiroshi
• Is Part Of: Arthritis & rheumatology. Volume 66:Issue 6(2014)
• Page Start: 1421
• Page End: 1431
• Publication Date: 2014-06
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.38400
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art38400-sec-0001" sec-type="section"> <title>Objective</title> <p>The aim of this prospective multicenter study was to identify biomarkers that can be used to predict therapeutic responses to tocilizumab in patients with rheumatoid arthritis (RA).</p> </sec> <sec id="art38400-sec-0002" sec-type="section"> <title>Methods</title> <p>We recruited patients with RA who were treated with tocilizumab for the first time, and determined therapeutic responses at 6 months. In the training cohort (n = 40), gene expression in peripheral blood mononuclear cells (PBMCs) at baseline was analyzed using genome‐wide DNA microarray, with 41, 000 probes derived from 19, 416 genes. In the validation cohort (n = 20), expression levels of the candidate genes in PBMCs at baseline were determined using real‐time quantitative polymerase chain reaction (qPCR) analysis.</p> </sec> <sec id="art38400-sec-0003" sec-type="section"> <title>Results</title> <p>We identified 68 DNA microarray probes that showed significant differences in signal intensity between nonresponders and responders in the training cohort. Nineteen putative genes were selected, and a significant correlation between the DNA microarray signal intensity and the qPCR relative expression was confirmed in 15 genes. In the validation cohort, a significant difference in relative expression between nonresponders and responders was reproduced for 3 type I interferon response genes (<italic>IFI6, MX2, </italic> and <italic>OASL</italic>) and <italic>MT1G</italic>. Receiver operating characteristic curve analysis of models incorporating these genes showed that the maximum area under the curve was 0.947 in predicting a moderate or good response to tocilizumab in the validation cohort.</p> </sec> <sec id="art38400-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Using genome‐wide DNA microarray analyses, we identified candidate biomarkers that can be used to predict therapeutic responses to tocilizumab in patients with RA. These findings suggest that type I interferon signaling and metallothioneins are involved in the pathophysiology of RA.</p> </sec> </abstract>