Exploration of predictive markers of therapeutic response to anti-IL-12/23p40 antibody in patients with Crohn's disease.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16992
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kyushu University
• Principal Investigator: Fujioka Shin 九州大学, 大学病院, 助教 (90814400)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: クローン病 / 抗IL-12/23p40抗体 / Th分化 / 遺伝子発現解析

Outline of Final Research Achievements

In this study, we analyzed changes in Th differentiation in peripheral blood T cells from Crohn's disease patients newly inducted anti-IL-12/23p40 antibody therapy. Gene expression analysis in intestinal mucosal tissues was also performed. The same analysis was performed on patients newly inducted anti-TNFα antibody therapy, and the two groups were compared. The results showed a significant decrease in the ratio of Th17 cells in peripheral blood in the group of patients treated with anti-IL-12/23p40 antibody. In addition, gene expression related to Th17 differentiation was suppressed in the intestinal mucosa tissue. The suppressed genes were differeant from those altered by anti-TNFα antibody therapy.

Free Research Field

医歯薬学

Academic Significance and Societal Importance of the Research Achievements

クローン病をはじめとした炎症性腸疾患では現在、複数の生物学的製剤および免疫抑制薬が治療薬として承認されているが、治療効果の予測因子や治療薬導入の順序は明らかとなっておらず、治療戦略を立てる上での障害となっている。本研究により抗IL-12/23p40抗体療法と抗TNFα抗体療法では異なる治療メカニズムを有していることが確認され、本研究で用いた分子生物学的手法が治療薬を選択する上での判断材料になる可能性が示された。さらに、それぞれの治療不応時や効果減弱時における薬剤の切り替えが有望な治療選択肢であることが裏付けられた。