Evaluation of High-Mobility Group Box 1 Protein Concentration in Serum of Patients withM. tuberculosisInfection

Abstract

Infection with Mycobacterium tuberculosis is accompanied by an intense inflammatory response. Recently, a new mediator of inflammation, HMGB1 protein has been identified that contributes to acute lung injury. However, its role in the systemic inflammatory response in tuberculosis has not been thoroughly investigated. We investigated the systemic levels of HMGB1 and TNF-α in patients with active and latent lung tuberculosis as a prognostic marker of disease activity. The study was performed to 70 patients with confirmed Mycobacterium tuberculosis infection and other than tuberculosis lung diseases and in 20 healthy persons. Serum HMGB1 and TNF-α concentrations were measured by ELISA. The highest concentration of HMGB1 was detected in the bloodstream of people with Mtb infection (latent and active). Its concentration increased significantly in sera of patients with active tuberculosis (47.5 ng/ml), compared to patients with other lung diseases (36.87 ng/ml). TNF-α had significantly higher concentration in a patients group compared to healthy controls, with the highest concentration in the LTBI group of patients (0.136 ng/ml). We observed a strong positive correlation between TNF-α and HMGB1 concentrations in patients with tuberculosis infections. We conclude that HMGB1 is secreted during active and latent tuberculosis in the highest amounts compared to other lung diseases.

Down-Regulation of Serum High-Mobility Group Box 1 Protein in Patients with Pulmonary Tuberculosis and Nontuberculous Mycobacterial Lung Disease

“…In previous reports, HMGB1 level was significantly increased in patients with TB compared with HC (TB patients vs. HC, 47.5±26.1 ng/mL vs. 13.8±7.3 ng/mL; roughly 2.2 ng/mL vs. 1.3 ng/mL [mean values not shown], respectively)1112. There was a large difference between the HMGB1 levels between the two studies.…”

“…Several studies have described the roles of HMGB1 in pathological states, including atherosclerosis, arthritis, acute lung injury, and bacterial pneumonia8910. A few papers have reported that the serum level of HMGB1 was increased in patients with tuberculosis (TB)1112. However, only limited information is currently available about the role of HMGB1 in TB infection.…”

HMGB1/RAGE Signaling and Pro-Inflammatory Cytokine Responses in Non-HIV Adults with Active Pulmonary Tuberculosis

“…IL-1β, IL-10, TNF-α) can be challenging; and circulating ‘receptor-bound’ HMGB1 (e.g. bound to soluble RAGE) cannot be measured accurately with the current assays [ 16 , 20 , 25 , 26 ]. As such, gene expressions were also studied.…”

“…bovis BCG [ 19 ] can effectively induce secretion of HMGB1, leading to cytokine hyperactivation and lung tissue damage. Recently, increased HMGB1 in serum of MTB-infected patients is reported but its significance is uncertain [ 20 ]. In the current study, we hypothesized that HMGB1/RAGE signaling and the pro-inflammatory cytokine responses play significant roles in pathogenesis and disease manifestations in patients with active pulmonary tuberculosis (PTB).…”

Nuclear Factor κB Activation Pathways During Infection

“…92 TLR2 also recognizes DAMPs, such as HMGB1 released from necrotic cells, representing a mechanism that regulates apoptosis during M. tuberculosis infection. 33,93,94 TLR4 recognizes the mycobacterial HSP, mitochondrial 50S ribosomal protein, and 38-kDa glycoproptein. [95][96][97][98] TIR domain-containing adaptor-inducing interferon β/MyD88 signaling is responsible for NF-κB activation in response to M. tuberculosis Hsp70-mediated activation of DCs.…”