Transforming growth factor-β and matrix metalloproteinases as potential biomarkers of fibrotic lesions induced by tuberculosis: a systematic review and meta-analysis

• Published in: BMJ open 2023-10, Vol.13 (10), p.e070377-e070377
• Main Authors: Santoso, Arif, Rasiha, Rasiha, Zainal, Ahmad Taufik Fadillah, Khairunnisa, Indah Nurul, Fais, Muthia Kintan, Gunawan, Andi Muh Aunul Khaliq
• Format: Article
• Language: English
• Subjects: Bias; Biomarkers; Fibroblasts; Growth factors; Meta-analysis; Patients; Pulmonary fibrosis; Respiratory infections; Respiratory Medicine; Respiratory physiology; Statistical analysis; Systematic review; Tuberculosis
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2022-070377

ObjectivesVery few studies and limited information are available regarding the mechanism of fibrosis in tuberculosis (TB). This study aimed to identify, describe and synthesise potential biomarkers of the development of tissue fibrosis induced by TB through a systematic method and meta-analysis.MethodsA literature search was performed using keywords according to the topic from electronic databases (ScienceDirect and PubMed) and other methods (websites, organisations and citations). Studies that matched predetermined eligibility criteria were included. The quality assessment tool used was the Quality Assessment of Diagnostic Accuracy Score 2, and the data obtained were processed using Review Manager V.5.3.ResultsOf the 305 studies, 7 met the eligibility criteria with a total sample of 365. The results of the meta-analysis showed that the post-TB group of patients with pulmonary parenchymal fibrosis had a higher transforming growth factor (TGF)-β level (6.09) than the control group (1.82), with a 4.27 (95% CI: 0.92 to 7.61) mean difference. Moreover, patients with residual pleural thickening post-TB had a higher mean of TGF-β (0.61) than the control group (0.56), with a 0.05 (95% CI: 0.04 to 0.06) mean difference. Besides TGF-β, our qualitative synthesis also found that matrix metalloproteinase-1 might have a role in forming and developing pulmonary tissue fibrosis, thus, could be used as a predictor marker in the formation of fibrotic lesions in patients with TB. In addition, several other biomarkers were assessed in the included studies, such as tumour necrosis factor-α, interleukin (IL)-4, IL-8, IL-10, plasminogen activator inhibitor-1 and platelet-derived growth factor. However, this study is not intended to examine these biomarkers.ConclusionsThere were differences in the results of TGF-β levels in patients with fibrotic lesions compared with controls. TGF-β might be a biomarker of fibrotic tissue formation or increased pulmonary tissue fibrosis in post-TB patients. However, further studies are needed on a larger scale.