可溶性T细胞免疫球蛋白粘蛋白结构域3在鉴别非结核分枝杆菌肺病与肺部定植中的作用

Role of Soluble T-Cell Immunoglobulin Mucin Domain-3 in Differentiating Nontuberculous Mycobacterial Lung Disease from Pulmonary Colonization.

作者信息

Pan Sheng-Wei, Shu Chin-Chung, Lee Chang-Ching, Feng Jia-Yih, Chan Yu-Jiun, Chen Yuh-Min, Su Wei-Juin

机构信息

Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; Institute of Public Health, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Arch Bronconeumol (Engl Ed). 2021 Feb 24. doi: 10.1016/j.arbres.2021.01.035.

DOI:10.1016/j.arbres.2021.01.035

PMID:33745754

Abstract

BACKGROUND

Differentiating between nontuberculous mycobacterial lung disease (NTM-LD) and pulmonary NTM colonization (NTM-Col) is difficult. Compared with healthy controls, patients with NTM-LD generally present immune tolerance along with increased expressions of T-cell immunoglobulin mucin domain-3 (TIM-3) and programmed cell death-1 (PD-1) on T lymphocytes. However, the role of soluble TIM-3 (sTIM-3) and soluble PD-1 (sPD-1) in differentiating NTM-LD from NTM colonization (NTM-Col) remains unclear.

METHODS

Patients with NTM-positive respiratory samples and controls were enrolled from 2016 to 2019. Patients were classified into NTM-Col and NTM-LD groups. Levels of sTIM-3, sPD-1, soluble PD-ligand-1 (sPD-L1), and TIM-3 expression were measured. Factors associated with NTM-LD were analyzed by logistical regression.

RESULTS

TIM-3 expression on CD4 and CD8 T lymphocytes were highest in NTM-LD group, followed by NTM-Col, and control (P=.017 and P=.011 for trend). sTIM-3 elevated in the NTM-Col group compared with the NTM-LD and control groups (856.3±518.7 vs. 595.3±352.6pg/mL, P=.009; vs. 437.0±267.4pg/mL, P<.001). Levels of sPD-1 and sPD-L1 were similar among groups. Among the 79 NTM-positive patients, sTIM-3 was associated with NTM-LD (100-pg/mL increase, adjusted odds ratio (aOR) 0.658 [95% CI, 0.502-0.864], P=.003). Patients with ≥2 risk factors (sTIM-3≤530pg/mL, BMI≤22.5, and radiographic score ≥5) were 13 times more likely to exhibit NTM-LD than those without (aOR 13.234 [2.983-58.709], P=.001).

CONCLUSIONS

sTIM-3 was an independent factor for differentiating NTM-LD from NTM-Col, suggesting the immunologic role of sTIM-3 in NTM-LD pathogenesis. By assessing sTIM-3 levels and other risk factors, physicians may be able to identify NTM-LD cases in a simplified manner.

摘要

背景

区分非结核分枝杆菌肺病（NTM-LD）和肺部非结核分枝杆菌定植（NTM-Col）具有挑战性。与健康对照相比，NTM-LD患者通常表现出免疫耐受，同时T淋巴细胞上的T细胞免疫球蛋白粘蛋白结构域3（TIM-3）和程序性细胞死亡蛋白1（PD-1）表达增加。然而，可溶性TIM-3（sTIM-3）和可溶性PD-1（sPD-1）在区分NTM-LD与NTM定植（NTM-Col）中的作用仍不清楚。

方法

2016年至2019年纳入非结核分枝杆菌阳性呼吸道样本患者及对照。患者分为NTM-Col组和NTM-LD组。检测sTIM-3、sPD-1、可溶性PD配体1（sPD-L1）水平及TIM-3表达。采用逻辑回归分析与NTM-LD相关的因素。

结果

NTM-LD组CD4和CD8 T淋巴细胞上的TIM-3表达最高，其次是NTM-Col组和对照组（趋势P值分别为0.017和0.011）。与NTM-LD组和对照组相比，NTM-Col组sTIM-3升高（856.3±518.7 vs. 595.3±352.6pg/mL，P=0.009；vs. 437.0±267.4pg/mL，P<0.001）。各组间sPD-1和sPD-L1水平相似。在79例非结核分枝杆菌阳性患者中，sTIM-3与NTM-LD相关（每增加100-pg/mL，调整后的比值比（aOR）为0.658 [95%CI，0.502-0.864]，P=0.003）。有≥2个危险因素（sTIM-3≤530pg/mL、BMI≤22.5和影像学评分≥5）的患者发生NTM-LD的可能性是无危险因素患者的13倍（aOR 13.234 [2.983-58.709]，P=0.001）。