Abstract
Effective control of Mycobacterium tuberculosis (Mtb) infection is mediated by multifaceted factors that involve both the endocrine and immune system. Profiling hormones and antibodies in different stages of TB provides insight in the pathogenesis of the disease. In this study, we profiled endocrine hormones (dehydroepiandrosterone (DHEA), cortisol, testosterone, estradiol, growth hormone and leptins) and Mtb strain H37RV lipoarabinomannan (LAM)-specific antibody levels in plasma samples, collected from pulmonary TB (PTB) patients, TB lymphadenitis (TBLN) patients and latently infected (QFT-positive) or uninfected (QFT-negative) apparently healthy individuals using ELISA. Plasma levels of leptin and DHEA were significantly low in PTB and TBLN patients compared to healthy controls (P<0.0001 and P=0.02, respectively), whereas these levels significantly increased following anti-TB treatment (P=0.002 and P=0.0001, respectively) among TB patients. The levels of estradiol and testosterone significantly improved following anti-TB treatment (P=0.03 and P=0.0003, respectively), whereas cortisol and growth hormones declined significantly (P <0.05). Similarly, LAM-specific IgG, IgM and IgA were significantly higher in PTB patients compared to other groups, whereas levels of IgG1 subtype were significantly higher among LTBI groups compared to both TB patients and QFT-negative individuals (P<0.0001). Overall, we observed significantly variable levels of endocrine hormones as well as immunoglobulins across the spectrum of TB illness and such profiling has a significant contribution in selection of effective biomarkers that have roles in TB treatment monitoring or diagnostics. Although this study did not show a functional association between hormones and antibodies, alterations in the levels of these biomarkers suggest the key roles these markers play in TB pathogenesis.
Highlights
The spectrum of tuberculosis (TB) pathogenesis often lies on interplay between the bacterium causing the illness, Mycobacterium tuberculosis (Mtb), and the host defense system, which is maneuvered by cells of the immune system
Plasma cortisol level was significantly higher in pulmonary TB (PTB) and TB lymphadenitis (TBLN) patients compared to apparently healthy groups, while its level was even higher in PTB patients compared to the TBLN cases (Figure 1C)
Though cell-mediated immunity demonstrates a major role in protection against TB, antibodies are recently reported to play a significant role in bacterial clearance and enhanced phagolysosomal maturation during TB infection [7]
Summary
The spectrum of tuberculosis (TB) pathogenesis often lies on interplay between the bacterium causing the illness, Mycobacterium tuberculosis (Mtb), and the host defense system, which is maneuvered by cells of the immune system In both experimental models and human patients, hormones are shown to act as immunomodulators and play a significant role in the pathogenesis of a disease [1]. Antibody responses are often regarded as inferior to cell-mediated immunity, their role in protection against TB has been demonstrated in several studies [5–9] Profiling these two components of the body’s defense system across a spectrum of TB illness is important to better understand TB pathogenesis and provide an additional insight to the ongoing biomarker pool investigations in TB control efforts. Its repetitive D-arabinofuranose residues allows it to direct B cell stimulatory functions [12], making it a suitable antigen choice in our study
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