Analysis of drug-HLA binding structures in severe drug eruptions and development of drugs for severe drug eruptions

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K08277
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53050:Dermatology-related
• Research Institution: Showa University
• Principal Investigator: Watanabe Hideaki 昭和大学, 医学部, 教授 (80327931)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 重症型薬疹 / HLA / バイカリン / Annexin A1 / スティーヴンス・ジョンソン症候群 / 中毒性表皮壊死症 / 薬剤性過敏症症候群

Outline of Final Research Achievements

Several drugs with frequently reported drug eruptions were expected to cause severe drug eruptions in individuals with HLA-B*13:01 due to their common structure with aromatics and a double bonded oxygen near the aromatics.
We found that baicalin inhibits cell death by blocking the binding of Annexin A1 and FRP1, which are involved in cell death in severe drug eruption SJS/TEN, and inhibiting the activation of RIP1 and RIP3, and thus may be a candidate for the treatment of SJS.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

薬剤を投与する前にHLAを測定することで死亡率の高いSJS/TEN（SJSで4%、TENで30%）の発症を抑える、いわゆるオーダーメード医療に繋がる。また現在SJS/TENの治療にはステロイド全身投与以外にいい治療法が無いのが現況であるが、漢方薬バイカリンが、SJS/TENにおいて皮膚の細胞死を阻害する可能性を見出し、SJSの治療薬の候補となりうることがわかり、今後の臨床応用に繋がる研究である。