Li Fuxiang, Zhu Chuanzhi, Zhang Yue, Kong Fanhui, Zhang Ximeng, Pan Liping, Jia Hongyan, Fu Liang, Hu Yunlong, Deng Guofang, Yang Qianting, Chen Xinchun, Cai Yi
Guangdong Provincial Key Laboratory of Infection Immunity and Inflammation, Department of Pathogen Biology, Shenzhen University Medical School, Shenzhen, China.
Department of Biochemistry, Center for Molecular Biomedicine, Friedrich Schiller University Jena, Jena, Germany.
JCI Insight. 2024 Dec 6;9(23):e185307. doi: 10.1172/jci.insight.185307.
BACKGROUNDCurrent diagnostic tools for tuberculous pleural effusion (TPE) are often inadequate, making accurate diagnosis challenging. Effective identification of TPE is critical for ensuring proper treatment and preventing tuberculosis relapse. This study explored the potential of granzyme A (GZMA) as a biomarker for TPE.METHODSPatients with TPE, malignant pleural effusion (MPE), and parapneumonic pleural effusion (PPE) were recruited into discovery and validation cohorts. The discovery cohort consisted of 200 patients with TPE and 100 patients with MPE, while the validation cohort included 167 patients with TPE, 84 patients with MPE, and 69 patients with PPE.RESULTSIn the discovery cohort, GZMA levels were significantly elevated in TPE compared with MPE, demonstrating 90% sensitivity and 91% specificity at a cutoff of 102.29 ng/mL for effectively distinguishing between the two conditions. In the validation cohort, GZMA maintained high diagnostic performance, distinguishing TPE from MPE with 87% sensitivity and 87% specificity and from PPE with 87% sensitivity and 84% specificity. Incorporating GZMA, lactate dehydrogenase (LDH), and adenosine deaminase (ADA) into a random forest model further improved diagnostic accuracy. In the discovery cohort, this model achieved 92% sensitivity and 100% specificity, and in the validation cohort, it distinguished TPE from MPE with 87% sensitivity and 94% specificity and from PPE with 87% sensitivity and 91% specificity.CONCLUSIONOverall, GZMA is a promising biomarker for diagnosing TPE, with improved accuracy when combined with LDH and ADA, providing a robust tool for timely identification and effective management of patients with TPE.FUNDINGThe study was supported by Science and Technology Project of Shenzhen (KCXFZ20211020163545004, KQTD20210811090219022, JCYJ20220818095610021, JSGG20220822095200001, JCYJ20210324094614038), Shenzhen Medical Research Funding (B2302035, A2302004), Provincial Natural Science Foundation of Guangdong (2022A1515220034), and Shenzhen Third People's Hospital Research Foundation (G2022155).
背景
目前用于结核性胸腔积液（TPE）的诊断工具往往不足，使得准确诊断具有挑战性。有效识别TPE对于确保适当治疗和预防结核病复发至关重要。本研究探讨了颗粒酶A（GZMA）作为TPE生物标志物的潜力。
方法
将TPE、恶性胸腔积液（MPE）和类肺炎性胸腔积液（PPE）患者纳入发现队列和验证队列。发现队列包括200例TPE患者和100例MPE患者，而验证队列包括167例TPE患者、84例MPE患者和69例PPE患者。
结果
在发现队列中，与MPE相比，TPE中的GZMA水平显著升高，在截断值为102.29 ng/mL时，有效区分这两种情况的灵敏度为90%，特异性为91%。在验证队列中，GZMA保持了较高的诊断性能，区分TPE与MPE的灵敏度为87%，特异性为87%，区分TPE与PPE的灵敏度为87%，特异性为84%。将GZMA、乳酸脱氢酶（LDH）和腺苷脱氨酶（ADA）纳入随机森林模型进一步提高了诊断准确性。在发现队列中，该模型的灵敏度为92%，特异性为100%，在验证队列中，区分TPE与MPE的灵敏度为87%，特异性为94%，区分TPE与PPE的灵敏度为87%，特异性为91%。
结论
总体而言，GZMA是一种很有前景的用于诊断TPE的生物标志物，与LDH和ADA联合使用时准确性更高，为及时识别和有效管理TPE患者提供了有力工具。
资助
本研究得到了深圳市科技计划项目（KCXFZ20211020163545004、KQTD20210811090219022、JCYJ20220818095610021、JSGG20220822095200001、JCYJ20210324094614038）、深圳市医学科研基金（B2302035、A2302004）、广东省自然科学基金（2022A1515220034）以及深圳市第三人民医院科研基金（G2022155）的支持。
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