Development of highly sensitive diagnostic method for latent tuberculosis infection in steroid-using patients

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K10024
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Infectious disease medicine
• Research Institution: Nagoya City University
• Principal Investigator: Maeda Tomoyo 名古屋市立大学, 医薬学総合研究院(医学), 研究員 (70782168)
• Co-Investigator(Kenkyū-buntansha): 前田 伸治 名古屋市立大学, 医薬学総合研究院(医学), 講師 (80381854)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 免疫抑制治療 / T細胞 / 潜在性肺結核診断

Outline of Final Research Achievements

An analysis was conducted on the mass cytometry data of peripheral blood T cells that had been cultured for 16-20 hours with the addition of tuberculosis-specific antigens from 20 patients with a history of tuberculosis under immunosuppressive treatment and 15 individuals not exposed to tuberculosis. It was observed that the positive rate of IFN-γ high cells within CD3+ T cells was elevated in the group with a history of tuberculosis. High-dimensional analysis was exclusively conducted on the fraction of IFN-γ positive cells. Both Cluster E, a CD4+ subset that expressed IL-2 at high levels with low GM-CSF, and Cluster H, a CD4+ subset expressing CD161 and CD25 surface antigens, were found to significantly increase in the IGRA positive group with a history of tuberculosis. These findings suggest the potential usefulness of these cell groups in the specific diagnosis of tuberculosis exposure in patients undergoing immunosuppressive treatment.

Free Research Field

膠原病

Academic Significance and Societal Importance of the Research Achievements

関節リウマチなどへの免疫抑制治療により医原性の結核蔓延が問題となるが、免疫抑制治療患者における結核特異的血液診断は、検査感度が著しく低下する。本研究により、免疫抑制治療中の結核既往リウマチ性疾患患者における、末梢血結核抗原特異的IFNγ産生T細胞の詳細なphenotypeが明らかとなった。免疫抑制下の結核免疫応答に重要なＴ細胞群の候補として、IFN-γhigh+CD４＋CXCR3＋IL-２high+TNF-α+T細胞、および、IFN-γhigh+CD4＋CD25＋CD161＋CXCR3＋T細胞が示された。これらの細胞群による新たな結核特異的診断法の開発が期待される。