Serum biomarkers in patients with unilateral or bilateral active pulmonary tuberculosis: Immunological networks and promising diagnostic applications

Tuberculosis is a chronic granulomatous disease transmitted via inhalation of aerosolized droplets carrying Mycobacterium tuberculosis (Mtb) that predominantly affects the lungs [1], [2], [3]. Pulmonary tuberculosis, besides being the most frequent (around 80 % of all cases) [3], is extremely relevant for public health, and represents a major public health problem worldwide. The World Health Organization estimates that 10 million people fall ill with TB and 1.5 million people die every year [1]. In Brazil, 66,819 new cases of TB were reported in 2020 [2].

In response to Mtb infection, several cytokine and chemokine are released by the host immune cells, playing a critical role in the host immune response against tuberculosis infection [4], [5], [6]. Due to these characteristics, severe pulmonary TB is considered an immunopathological disease developed due to immunological hyperreactivity and presents a nonspecific profile of pro-inflammatory cytokines and chemokines, extensive neutrophilic and macrophage infiltration, exacerbated T-cell responses according to the phase of infection, severity of disease evolution and response to anti-TB treatments [7], [8], [9], [10].

Moreover, the clinical outcome of Mtb infection is determined by a complex interaction of various cytokines that regulate the differentiation, proliferation, and activation of immune cells [11], [12]. To determine a biomarker profile, it is essential to investigate the cytokine/chemokine of TB patients and its role in the extension of lung involvement as well as the severity of the disease. The identification of a pattern of differentially expressed biomarkers (a “biosignature”) could help to diagnosis, in addition to evaluate the disease progression.

Another important aspect in the context of TB is the relationship among immunological aspects and radiological patterns, especially in the severe forms that progress to the development of pulmonary cavitation. In Brazil, a recent study shows the association of biomarker levels with cavitation, including patients who already had these alterations before the beginning of the TB treatment [13].

So, the aim of this study was to analyze multiple serum soluble immunological mediators to evaluate biosignatures in patients with active tuberculosis. Also, this study provides a thorough perspective on the connectivity of these biomarkers with the extension of lung involvement as well as the disease severity.

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