Calpain and spectrin breakdown products as potential biomarkers in tuberculous pleural effusion

Abstract

Background: Early diagnosis of tuberculous pleural effusion (TPE) remains difficult. Calpain is a family of calcium-dependent endopeptidase that plays an important role in extracellular matrix (ECM) remodeling and collagen synthesis. The aim of this study was to explore the diagnostic value of pleural fluid angiotensinconverting enzyme (ACE), calpain-1, spectrin breakdown products (SBDP), and matrix metalloproteinase-1 (MMP-1) in TPE and malignant pleural effusion (MPE). Methods: The study included 47 patients with TPE, 28 patients with MPE, and 10 patients with transudate of non-tuberculous and non-malignant origin as controls. Calpain-1, ACE, SBDP, and MMP-1 levels in pleural fluid were measured by the ELISA method. Results: ACE, calpain-1, SBDP, and MMP-1 levels were higher in TPE than MPE and transudate (all, P < 0.05). On multivariate logistic regression analysis, adenosine deaminase (ADA) ≥40 IU/mL, calpain-1 ≥787 ng/mL, and SBDP ≥2.745 ng/mL were independent factors associated with TPE. The predicted probability of TPE based on these three predictors had an area under the receiver operating characteristic (ROC) curve of 0.985, with 97.9% sensitivity and 86.6% specificity under a cut-off value of 0.326. In patients with TPE, residual pulmonary thickening (RPT) was associated with significantly higher calpain-1, SBDP, and MMP-1 levels (all, P < 0.05) versus cases without RPT. Conclusions: Our results suggest that the overproduction of calpain-1 and SBDP is associated with pleural fibrosis in tuberculous pleurisy. While ADA is a conventional marker for diagnostic TPE, the simultaneous measurement of calpain-1 and SBDP l in pleural fluid may improve the diagnostic efficacy.