Ren Jingjing, Qu Shengyan, Bian Keyun, Yao Min, Yao Fan, Xu Feifan, Zhang Rui
Department of Immunology, School of Medicine, Nantong University, Nantong, China.
Department of Clinical Laboratory, Affiliated Nantong Hospital of Shanghai University (The Sixth People's Hospital of Nantong), Nantong, China.
J Thorac Dis. 2025 Aug 31;17(8):6189-6200. doi: 10.21037/jtd-2025-1299. Epub 2025 Aug 26.
Unlike smear-positive tuberculosis (TB) which is more easily diagnosed due to the presence of (MTB) in sputum, smear-negative pulmonary tuberculosis (SN-TB) poses a diagnostic challenge that can lead to delayed treatment hence new molecular diagnostic markers are urgently needed. The aim of this study was to analyze the expression of CD101 in peripheral blood mononuclear cells (PBMCs), T cells and natural killer (NK) cells of patients with SN-TB through a case-control study and to assess the value of CD101 alone or combined with other cytokines in the auxiliary diagnosis of SN-TB.
Sixty-three newly treated patients with TB and negative smear results diagnosis by clinicians were included as the SN-TB group, while 59 healthy individuals [healthy control (HC)] were included as the control group. The expression of CD101 in PBMCs of the two groups was detected via real-time quantitative polymerase chain reaction (RT-qPCR). The expression of CD101 on T cells and NK cells, as well as the expression of T helper (Th) 1/2/17-related cytokines was detected by flow cytometry. Spearman analysis was used to analyze the correlation between CD101 expression, cytokines and clinical indicators in patients with SN-TB. Receiver operating characteristic (ROC) curve analysis was used to analyze the sensitivity and specificity of CD101 alone or in combination with other cytokines in diagnosing SN-TB.
Compared with the control group, the experimental group showed high CD101 expression in PBMCs and CD4 T cells but not in CD8 T cells or NK cells. Th1/Th2-related cytokines interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were highly expressed in patients with SN-TB, but there was no significant difference in the expression of the Th17-related cytokine (IL-17A). The expression of CD101 on CD4 T cells in patients with SN-TB was positively correlated with cytokines IL-2 and IFN-γ and the clinical indicators of ESR and CRP. CD101 on CD4 T cells could well distinguish patients with SN-TB from HC, with a sensitivity of 71.43%, a specificity of 71.19% and an area under the curve (AUC) of 0.7604. The sensitivity of CD101CD4 (%) combined with IL-2 was 73.25%, the specificity was 68.25% and the AUC was 0.7893. The sensitivity of CD101CD4 (%) combined with IFN-γ was 72.88%, the specificity was 66.67% and the AUC was 0.7678. The sensitivity of CD101CD4 (%) combined with IFN-γ and IL-2 was 74.58%, the specificity was 74.60% and the AUC was 0.7899.
The expression of CD101 on CD4 T cells could distinguish patients with SN-TB from healthy individuals and was correlated with key TB infection cytokines, including IL-2 and IFN-γ, as well as with ESR and CRP. CD101 demonstrated good diagnostic efficacy in combination with cytokines. It might thus be an indicator for laboratory-assisted diagnosis of SN-TB.
与因痰中存在结核分枝杆菌(MTB)而更易诊断的涂片阳性肺结核不同,涂片阴性肺结核(SN-TB)带来了诊断挑战,可能导致治疗延迟,因此迫切需要新的分子诊断标志物。本研究旨在通过病例对照研究分析SN-TB患者外周血单个核细胞(PBMC)、T细胞和自然杀伤(NK)细胞中CD101的表达,并评估CD101单独或与其他细胞因子联合在SN-TB辅助诊断中的价值。
纳入63例临床诊断为新治且涂片结果阴性的肺结核患者作为SN-TB组,纳入59例健康个体[健康对照(HC)]作为对照组。通过实时定量聚合酶链反应(RT-qPCR)检测两组PBMC中CD101的表达。采用流式细胞术检测T细胞和NK细胞上CD101的表达以及辅助性T(Th)1/2/17相关细胞因子的表达。采用Spearman分析SN-TB患者中CD101表达、细胞因子与临床指标之间的相关性。采用受试者工作特征(ROC)曲线分析CD101单独或与其他细胞因子联合诊断SN-TB的敏感性和特异性。
与对照组相比,实验组PBMC和CD4 T细胞中CD101表达较高,但CD8 T细胞或NK细胞中未出现此情况。SN-TB患者中Th1/Th2相关细胞因子白细胞介素-2(IL-2)、IL-4、IL-6、IL-10、肿瘤坏死因子-α(TNF-α)和干扰素-γ(IFN-γ)高表达,但Th17相关细胞因子(IL-17A)表达无显著差异。SN-TB患者CD4 T细胞上CD101的表达与细胞因子IL-2和IFN-γ以及血沉(ESR)和C反应蛋白(CRP)的临床指标呈正相关。CD4 T细胞上的CD101能够很好地区分SN-TB患者与HC,敏感性为71.43%,特异性为71.19%,曲线下面积(AUC)为0.7604。CD101CD4(%)联合IL-2的敏感性为