An exploratory study on the key molecules in Japanese autoimmune rheumatic diseases using genome and transcriptome analyses.

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670458
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: University of Tsukuba
• Principal Investigator: TSUCHIYA Naoyuki 筑波大学, 医学医療系, 教授 (60231437)
• Co-Investigator(Renkei-kenkyūsha): FURUKAWA Hiroshi 国立病院機構相模原病院, 臨床研究センター, 室長 (00372293) ; OHASHI Jun 東京大学, 理学系研究科, 准教授 (80301141)
• Research Collaborator: KAWASAKI Aya 筑波大学, 医学医療系, 助教 (30532816) ; HACHIYA Yuki 筑波大学, 大学院人間総合科学研究科
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 全身性エリテマトーデス / ANCA関連血管炎 / トランスクリプトーム / 遺伝子発現 / インターフェロン

Outline of Final Research Achievements

Transcriptome analyses reveal not only the key molecules in the pathogenesis, but also novel susceptibility genes which influence expression levels. Here we compared transcriptomes of Japanese patients with active systemic lupus erythematosus (SLE), ANCA-associated vasculitis (AAV) and healthy controls (HC). These groups were found to form distinct clusters. Significant enrichment of type I interferon related genes was detected not only in the differentially expressed genes in SLE, but also in AAV. Some of these genes exhibited opposite directions of expression change in SLE and AAV, suggesting that they might be related to the difference in the pathogenesis of these diseases. Furthermore, significant down-regulation of HLA class II genes was detected in AAV, suggesting that the molecular mechanism of association between HLA class II and AAV might involve reduced expression level. Thus, this exploratory study generated many testable hypotheses which should be validated in the future.

Free Research Field

膠原病学