Antigen-specific chemokine CCL3 as a biomarker for distinguishing between recent and remote tuberculosis infection.

IF 5.4 2区医学 Q1 INFECTIOUS DISEASES

Infection Pub Date : 2025-05-25 DOI:10.1007/s15010-025-02571-3

Chunyan Chang, Zichun Ma, Weicong Ren, Wei Wang, Haohan Liu, Rujie Zhong, Shanshan Li, Mengqiu Gao, Yu Pang

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引用次数: 0

Abstract

Background: Identifying recent tuberculosis (TB) infection individuals and administering TB preventive therapy (TPT) are critical strategies for controlling TB. However, current diagnostics fail to identify these individuals at high risk for developing active TB. Herein, we aimed to explore the candidate biomarkers to distinguish recent TB infection from remote TB infection individuals.

Methods: Close contacts of TB patients were continuously recruited. A total of 121 participants meeting study inclusion criteria were assigned to screening and validation cohorts, consisting of 45 participants assigned to screening cohort, and 76 participants assigned to validation cohort. The inflammation-related protein biomarkers in Mtb antigen-stimulated blood plasma were measured in the screening cohort using the Olink targeted proteomics. The candidate biomarkers were verified in validation cohort with the customized Luminex-based multiplex microbead array.

Results: Quantitative proteomics analysis reveals that significant differences in Mycobacterium tuberculosis (Mtb) antigen-stimulated blood plasma levels of CCL3, CCL20, CCL23 and TNF-α between remote and recent TB infection group. The different response profiles of memory immune cells to Mtb antigens could stem from activation of the NF-κB signaling pathway. The levels of CCL3, CCL20 and TNF-α were predictive of recent TB infection group, of which CCL3 exhibited the best performance with an AUC value of 0.859, yielding a sensitivity and specificity of 86.4% and 75%, respectively.

Conclusions: The Mtb antigen-specific assay utilizing CCL3 exhibits superior diagnostic performance and could potentially enhance diagnostic accuracy for identifying recent TB infection patients among LTBI individuals.

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抗原特异性趋化因子CCL3作为区分近期和远期结核感染的生物标志物。

背景：识别新近感染结核病的个体并实施结核病预防治疗（TPT）是控制结核病的关键策略。然而，目前的诊断方法无法识别这些发生活动性结核病的高危人群。在此，我们旨在探索候选的生物标志物，以区分近期结核感染和远程结核感染个体。方法：连续招募结核病患者密切接触者。符合研究纳入标准的121名受试者被分配到筛查和验证队列，其中45名受试者被分配到筛查队列，76名受试者被分配到验证队列。在筛查队列中，使用Olink靶向蛋白质组学测量结核分枝杆菌抗原刺激血浆中炎症相关蛋白生物标志物。候选生物标志物在验证队列中使用定制的基于luminex的多重微珠阵列进行验证。结果：定量蛋白质组学分析显示，结核分枝杆菌（Mtb）抗原刺激的血浆CCL3、CCL20、CCL23和TNF-α水平在远端和近期结核感染组之间存在显著差异。记忆免疫细胞对Mtb抗原的不同反应可能源于NF-κB信号通路的激活。CCL3、CCL20和TNF-α水平是近期结核感染组的预测指标，其中CCL3表现最佳，AUC值为0.859，敏感性和特异性分别为86.4%和75%。结论：利用CCL3的Mtb抗原特异性检测显示出优越的诊断性能，并可能提高LTBI个体中近期结核病感染患者的诊断准确性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Infection 医学-传染病学

CiteScore

12.50

自引率

1.30%

发文量

224

审稿时长

6-12 weeks

期刊介绍： Infection is a journal dedicated to serving as a global forum for the presentation and discussion of clinically relevant information on infectious diseases. Its primary goal is to engage readers and contributors from various regions around the world in the exchange of knowledge about the etiology, pathogenesis, diagnosis, and treatment of infectious diseases, both in outpatient and inpatient settings. The journal covers a wide range of topics, including: Etiology: The study of the causes of infectious diseases. Pathogenesis: The process by which an infectious agent causes disease. Diagnosis: The methods and techniques used to identify infectious diseases. Treatment: The medical interventions and strategies employed to treat infectious diseases. Public Health: Issues of local, regional, or international significance related to infectious diseases, including prevention, control, and management strategies. Hospital Epidemiology: The study of the spread of infectious diseases within healthcare settings and the measures to prevent nosocomial infections. In addition to these, Infection also includes a specialized "Images" section, which focuses on high-quality visual content, such as images, photographs, and microscopic slides, accompanied by brief abstracts. This section is designed to highlight the clinical and diagnostic value of visual aids in the field of infectious diseases, as many conditions present with characteristic clinical signs that can be diagnosed through inspection, and imaging and microscopy are crucial for accurate diagnosis. The journal's comprehensive approach ensures that it remains a valuable resource for healthcare professionals and researchers in the field of infectious diseases.