Elucidation of the pathogenic mechanism of autoimmune diseases focusing on HHV-6 persistent infection in DIHS

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08306
• 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: Nara Medical University
• Principal Investigator: Hideo Asada 奈良県立医科大学, 医学部, 教授 (60252681)
• Co-Investigator(Kenkyū-buntansha): 新熊 悟 奈良県立医科大学, 医学部, 准教授 (00613788) ; 森 康子 神戸大学, 医学研究科, 教授 (50343257)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 薬剤性過敏症症候群 / DIHS / ヒトヘルペスウイルス / HHV-6 / 持続感染 / 自己免疫疾患

Outline of Final Research Achievements

It is known that autoimmune diseases develop during the recovery period in DIHS, but the mechanism is unknown. We found that patients with persistent HHV-6 infection after DIHS develop autoimmune diseases at a high rate. In order to elucidate the mechanism of the development of autoimmune diseases in DIHS, we performed single-cell RNA sequencing analysis of PBMCs from the persistent infection group, which developed autoimmune diseases, and the transient group, which did not develop complications. As a result, we found that HHV-6 persists in CD4 central memory T cells in patients with persistent HHV-6 infection, and that there is a decrease in the number of monocyte-lineage cells and a decrease in gene expression related to phagocytosis and antigen presentation in the acute phase.

Free Research Field

皮膚科学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、DIHS後にHHV-6持続感染をきたし自己免疫疾患を発症した患者では、一過性感染患者と比較して、DIHS急性期に単球系細胞が減少し、貪食・抗原提示に関連する遺伝子発現の低下も認めたことから、発症早期の単球系細胞の機能低下がその後のHHV-6持続感染に関わっていることが示唆された。また、回復期にHHV-6がCD4 central memory T細胞に持続感染し、この細胞中で特定のHHV-6関連遺伝子の発現を認めたことからHHV-6持続感染T細胞が、自己免疫疾患の発症に何らかの役割を担っている可能性が推測され、本研究がDIHS後自己免疫疾患の解明に繋がるものと期待される。