Granzyme A as biomarker for diagnosis in tuberculous pleural effusion
Fuxiang Li, Chuanzhi Zhu, Yue Zhang, Fanhui Kong, Ximeng Zhang, Liping Pan, Hongyan Jia, Liang Fu, Yunlong Hu, Guofang Deng, Qianting Yang, Xinchun Chen, Yi Cai
Fuxiang Li, Chuanzhi Zhu, Yue Zhang, Fanhui Kong, Ximeng Zhang, Liping Pan, Hongyan Jia, Liang Fu, Yunlong Hu, Guofang Deng, Qianting Yang, Xinchun Chen, Yi Cai
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Clinical Research and Public Health Infectious disease

Granzyme A as biomarker for diagnosis in tuberculous pleural effusion

Abstract

BACKGROUND Current 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.METHODS Patients 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.RESULTS In 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.CONCLUSION Overall, 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.FUNDING The 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).

Authors

Fuxiang Li, Chuanzhi Zhu, Yue Zhang, Fanhui Kong, Ximeng Zhang, Liping Pan, Hongyan Jia, Liang Fu, Yunlong Hu, Guofang Deng, Qianting Yang, Xinchun Chen, Yi Cai

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Figure 4

Diagnostic performance of the RF model in an independent validation cohort.

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Diagnostic performance of the RF model in an independent validation coho...
(A–C) The levels of ADA, LDH, and GZMA in pleural effusions from the validation cohort (TPE, n = 167; MPE, n = 84; PPE, n = 69). Data are shown as the mean ± SEM, and differences among the 3 groups were analyzed using 1-way ANOVA with post hoc multiple comparisons (**P < 0.01; ***P < 0.001; ****P < 0.0001). P values of less than 0.05 were considered significant. (D) A total of 320 participants with clinical diagnosis results were independently validated using the established RF model, with the cutoff value set as 0.634 (indicated by a dotted line). (E) Confusion matrices comparing the diagnostic accuracy of ADA, LDH, and GZMA and the RF model for TPE, MPE, and PPE. The RF model shows enhanced performance.