Active <i>versus</i> latent pulmonary tuberculosis: which one is the appropriate distinguishing biomarker?

Abstract

This study tried to assess the possibility of using the estimated levels of plasma expression of microRNAs (miR-) for distinguishing healthy subjects with latent pulmonary tuberculosis (LTB) from healthy controls (HC) and patients with active tuberculosis (ATB). Study participants included 30 newly diagnosed ATB patients, 30 of the households of ATB patients who were free of clinical manifestations, had normal chest radiography but had positive results on the whole-blood QuantiFERON tuberculosis (TB) Gold In-Tube (QFT-GIT) test (LTB patients), and 30 HC who were free of clinical symptoms and showed normal chest X-rays and negative QFT-GIT tests. All participants gave blood samples for quantitation of the plasma expression levels of miR- using the reverse transcription-quantitative polymerase chain reaction. Plasma levels of miR-150-5p were significantly downregulated in ATB samples than in other samples. However, miR-155-5p and miR-378-5p were significantly overexpressed in patients' samples compared to HC's samples and in ATB samples compared to LTB samples. On the contrary, plasma miR-4523-5p showed significant upregulation in LTB samples compared to ATB and HC samples, indicating insignificant in-between differences. The receiver operating characteristic curve analysis showed the ability of the estimated levels of the four miR- to differentiate TB patients from HC. Multivariate regression analysis defined expression levels of miR-155-5p and miR-378-5p as the significant biomarkers for distinguishing TB patients and levels of miR-378-5p and miR-4523-5p for identification of LTB patients. Pulmonary TB induces deregulated expression of miR-, according to the infection severity. An estimation of the expression levels of miR-378-5p and miR-4523-5p might be a reliable combination for identifying LTB patients.