NEUTROPHILS’ ABILITY TO FORM NETS EX VIVO AND THE CITRULLINATED HISTONE H3 LEVELS IN BLOOD DURING THE PREVENTIVE CHEMOTHERAPY OF LATENT TUBERCULOSIS INFECTION
Authors:   Omsk State Medical University, NOVIKOV DMITRIJ G. , ZOLOTOV ALEXANDER N. ,   Omsk State Medical University, MORDYK ANNA V. ,   Omsk State Medical University, INDUTNY ANTON V. ,   Omsk State Medical University, KIRICHENKO NIKOLAJ А. ,   Omsk State Medical University, ROMANOVA MARIYA А. ,   Omsk State Medical University, PTUKHIN ALEXANDER О. ,   Omsk State Medical University
Published: December 2024

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.