Biomarker to predict treatment efficacy of MAC pulmonary disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 17K10023
• 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: Yutaka Ito 名古屋市立大学, 医薬学総合研究院(医学), 准教授 (80362482)
• Co-Investigator(Kenkyū-buntansha): 新實 彰男 名古屋市立大学, 医薬学総合研究院(医学), 教授 (30252513)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Keywords: Mycobacterium avium / LL-37 / 好中球 / IL-8 / 抗菌活性 / CT / 菌陰性化

Outline of Final Research Achievements

Among 18 patients of pulmonary MAC disease who received multidrug treatment for more than 12 months, LL-37 in bronchoalveolar lavage (BAL) was associated with improvement of CT findings, but not bacterial negative conversion. LL-37 in BAL was positively correlated with neutrophil rate and IL-8 in BAL. The improvement of CT findings was not associated with neutrophil rate and IL-8 in BAL, age, white blood cell counts and neutrophil counts in blood and CRP. LL-37 in BAL was the only biomarker to predict the improvement of CT findings. The MICs of MAC bacilli for clarithromycin, rifampicin, and ethambutol in the presence of LL-37 were significantly reduced. LL-37 enhanced antimicrobial effects.

Free Research Field

感染症内科

Academic Significance and Societal Importance of the Research Achievements

LL-37は好中球から産生されると報告されており、MAC菌感染により惹起された気管支、肺内の好中球性炎症に関連して産生されたLL-37が、その抗菌薬の増強効果により画像所見の改善という臨床効果につながったと考えられ、LL-37は治療効果を予測するバイオマーカーになる可能性が示された。治療前喀痰培養陰性の軽症例が多く、菌陰性化との関連を示せなかったのが本研究の限界ではあるが、LL-37が低値で抗菌治療による画像所見の改善が乏しい症例でのLL-37補充療法という新たな治療の可能性をみいだした。