NEUTROPHILS’ ABILITY TO FORM NETS EX VIVO AND THE CITRULLINATED HISTONE H3 LEVELS IN BLOOD DURING THE PREVENTIVE CHEMOTHERAPY OF LATENT TUBERCULOSIS INFECTION

Introduction. Assessment of changes in the cellular link of innate immunity can enhance the informativeness of approaches to the diagnosis of latent tuberculosis infection. The process of forming neutrophil extracellular traps, NETosis, was described relatively recently, and there is no information in scientific publications about changes in neutrophils’ NETosis ability during preventive chemotherapy in latent tuberculosis infection. Aim. To determine the ability of peripheral blood neutrophils to form extracellular traps ex vivo, and the contents of citrullinated histone H3, PAD4, dynamin–like protein–1, and interleukins 1 and 8 in blood after a 6–month course of preventive chemotherapy for latent tuberculosis infection in children. Materials and Methods. Peripheral blood neutrophils’ ability to form extracellular traps after exposure to a nonspecific antigenic stimulant was studied, as well as the concentrations of citrullinated histone H3, Peptidyl arginine deiminase 4, dynamin–like protein–1, and interleukins 1 and 8 in blood. Group 1 (“Control”) included 30 healthy children with negative tuberculin reaction to tuberculin. Group 2 included 27 children with latent tuberculosis infection, having a positive tuberculosis recombinant allergen test reaction. In this group, all studies were performed at two study points: Point 1 – at the time of initial detection of the infection, point 2 – 6 months after the start of preventive chemotherapy. Results and Discussion. Neutrophils’ ability to form extracellular traps in Group 2 at Point 1 was significantly higher compared to that in the Control Group, with neutrophils more often forming filamentous traps (p=0.0419). After preventive chemotherapy (Point 2), we observed a decrease in the proportion of thread traps (p=0.0357) to the level of the Control Group (p=0.0724). The content of citrullinated histone H3 in the blood of patients from Group 2 at Point 1 was Me=5.60 (Q1=2.80; Q3=12.00) and, statistically, significantly higher (p=0.0002) as compared to the values of the Control Group: Me=1.41 (Q1=0.91; Q3=1.78). In preventive chemotherapy, the analyte concentration decreased: Me=1.20 (Q1=0.90; Q3=1.50), reaching the values that did not differ from those observed in the Control Group. Examining the concentrations of PAD4, dynamin–like protein–1, and interleukins 1 and 8 in blood did not reveal statistically significant differences between the groups studied. Conclusions. In the preventive chemotherapy of latent tuberculosis infection against the background of achieving positive clinical results, normalization of neutrophils’ ability to form extracellular traps was observed, and the proportion of filamentous traps decreased. Decrease in the citrullinated histone H3 content in the blood probably indicated weakening of the intensity of nephrosis. These indicators can be considered as probable and promising markers of the positive results of the chemotherapy of latent tuberculosis infection.