Study of pathological condition of DIHS focusing on virus-derived microRNA and development of new diagnostic method

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K10250
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Nara Medical University
• Principal Investigator: ASADA HIDEO 奈良県立医科大学, 医学部, 教授 (60252681)
• Co-Investigator(Kenkyū-buntansha): 宮川 史 奈良県立医科大学, 医学部, 講師 (00346024)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 薬剤性過敏症症候群 / DIHS / ヒトヘルペスウイルス / HHV-6 / 再活性化 / 持続感染 / microRNA / 薬疹

Outline of Final Research Achievements

Involvement of HHV-6 in the pathogenesis of DIHS has been suggested, but much remains unknown. Recently, it has been suggested that herpesvirus-derived microRNAs (miRNAs) are involved in the maintenance of latent infection and reactivation of herpesviruses. Therefore, we aimed to elucidate the pathogenesis of DIHS by identifying and analyzing HHV-6-derived miRNAs expressed in DIHS. We found that hhv6b-miR-Ro6-2 and -3, which are encoded in antisense of HHV-6 immediate early gene, were detected in serum and mononuclear cells during the acute phase of DIHS, and their expression was significantly correlated with clinical symptoms, suggesting that at least some HHV-6-derived miRNAs may be intimately involved in the pathogenesis of DIHS.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、HHV-6由来miRNAの1つであるhhv6b-miR-Ro6-2の発現が、HHV-6の再活性化（HHV-6 DNAの出現）に先行してみとめられたことから、DIHSの早期診断マーカーのとなり得ることが判明した。さらにhhv6b-miR-Ro6-2のレベルが皮疹重症度、発熱期間、DRESS scoreと相関していたことから病勢把握にも役立つ可能性が示された。また、4種類のmicroRNAはそれぞれ異なる発現パターンを示したことから、DIHSの病態において異なる役割を担っている可能性が示唆された。