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

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 angiotensin-converting enzyme (ACE), calpain-1, spectrin breakdown products (SBDP), and matrix metalloproteinase-1 (MMP-1) in TPE and malignant pleural effusion (MPE).

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.

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.

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.