Coronary heart disease remains the leading cause of death worldwide, requiring a study of its pathogenesis in view of the immunothrombosis concept. A key role in these events is attributed to neutrophil extracellular traps, with citrullinated histone H3a being a highly specific marker The systemic levels of H3a have been insufficiently studied in various forms of coronary heart disease. Objective of the present work was to compare the level of circulating CitН3 in the groups of patients with acute myocardial infarction complicated by coronary occlusions; patients with stable ischemic heart disease, and generally healthy individuals. The study included patients with acute myocardial infarction with occlusion of the coronary arteries (group 1), stable ischemic heart disease (group 2), and generally healthy individuals matched for gender and age. The level of CitН3 in the blood serum was determined by enzyme-linked immunosorbent assay. Statistical processing was performed using the StatTech software. The highest CitН3 level was detected in patients of group 2 (median 8500 ng/mL), which was significantly higher than the values in patients with acute myocardial infarction (p = 0.004). In group 1, the CitН3 concentration (median 3000 ng/mL) was lower than in the control (4650 ng/ mL), but the differences did not reach statistical significance. An inverse correlation was revealed between the CitН3 level and the white blood cell counts (ρ = -0.612; p = 0.002). ROC analysis confirmed that CitН3 is a statistically significant predictor for differentiating stable and acute coronary heart disease (AUC = 0.875; p = 0.003). The systemic CitН3 level varies significantly in different forms of coronary heart disease. The paradoxically low CitН3 concentration in myocardial infarction is likely explained by its local deposition in the area of coronary thrombosis. High CitН3 levels in stable myocardial infarction may reflect chronic immunothrombosis and subclinical inflammation, making this marker a promising tool for risk stratification and disease activity assessment.
Severe stress is known to cause dysfunction of immune, neuroendocrine, cardiovascular, digestive, and other systems. This is particularly true in inflammatory bowel diseases, where psychological stress is associated with exacerbation of the disease, as shown both in clinical settings and in experimental animals. For example, in a murine model with prolonged psychological stress caused by restricted movement and induced colitis, the stress factor was shown to exacerbate intestinal inflammation, as confirmed by colonoscopy, histology, fecal lipocalin levels, and increased expression of proinflammatory cytokine genes in the colon. One should note that the production of proinflammatory cytokines is linked to the functioning of Toll-like receptors, which expression can be modified by stress. The aim of this study was to determine, whether chronic stress affects the expression of Toll-like receptors 2 and 4 (TLR2 and TLR4) and proinflammatory cytokine tumor necrosis factor α (TNFα) genes in intestinal cells without additional induction of the inflammatory process. Moreover, we studied the potential of human lactoferrin to modify expression of these genes. Lactoferrin is a multifunctional glycoprotein of the transferrin family, which has been shown to have immunomodulatory, anti-inflammatory and stress-protective properties. A chronic stress in rats was modeled by forced swimming in cold water (2-4 °C) for 2 minutes daily for 11 days. The rats were simultaneously given human lactoferrin per os at a dose of 200 μg/kg body weight. TLR4, TLR2, and TNFα genes expression was assessed using real-time polymerase chain reaction. The study demonstrated that after 12 days after exposure to stress, the expression of TLR4, TLR2, and TNFα genes increased in intestinal cells. Daily oral administration of human lactoferrin reduced this expression. Administration of lactoferrin in absence of stress did not alter the expression of the studied genes. These data indicate activation of genes responsible for the proinflammatory response in the intestine during chronic stress and the possibility of modulating the activity of these genes by oral low-dose administration of human lactoferrin. Thus, human lactoferrin may be used as an immunomodulator to prevent stress-induced inflammatory processes in the intestine.
ADAM (A Disintegrin And Metalloproteinase) proteases, or adamalizins, are a family of protein peptidases that cleave the ectodomains of membrane proteins. The leading place in this family, both in terms of the level of protease activity and the spectrum of cleaved substrates, is given to two proteases – ADAM10 and ADAM17, which are similar in structure and partially overlap in substrate specificity. ADAM10/ADAM17 targets include growth factors, cytokines, cytokine receptors, adhesion molecules, and apoptotic molecules. The mechanisms of ADAM-dependent regulation are complex and diverse: the same protease can cause both the blockade of cleaved factors (FasL) or the processes induced by them (IL-1R, TNFR1, Fas receptors), and their activation (TNF, IL-15R), not to mention the fact that the cleaved factors themselves can play both a positive and a negative role in the development of the disease. A significant portion of ADAM10/ADAM17 targets are involved in the development of autoimmune inflammation – the association of these adamalizins with the development of type 1 diabetes mellitus, rheumatoid arthritis, autoimmune thyroiditis, and systemic lupus erythematosus has been convincingly demonstrated. The aim of this work was to analyze the contribution of ADAM10 and ADAM17 proteases to the development of myasthenia gravis, an autoimmune neurological disease associated with impaired neuromuscular transmission. The main targets of the autoimmune attack in this pathology are proteins of the postsynaptic membrane of the neuromuscular synapse-acetylcholine receptors and, to a much lesser extent, muscle-specific tyrosine kinase, lipoprotein receptor protein 4, as well as extrasynaptic proteins. Although autospecific antibodies play a key role in the pathogenesis of myasthenia gravis, T lymphocytes are the central link that ensures an effective humoral response to autoantigens and participates in the development of autoimmune inflammation. According to the analysis, there is currently no data confirming a direct link between ADAM10/ADAM17 proteases and the development of myasthenia gravis. However, since a significant portion of the targets of these adamalizins are involved to a greater or lesser extent in the pathogenesis of myasthenia gravis, in particular in the control of T cell activity and T-dependent B cell activation, ADAM10/ADAM17 can be considered as potential integral regulators in this pathology.
Software for assessing immune status of patients has been proposed by a team of authors from Krasnoyarsk Scientific Center of the Siberian Branch of RAS). The calculations are made on the basis of estimated blood leukogram parameters. The software has shown its effectiveness in various pathological conditions. Of special interest are the studies of proposed method for assessing the dynamics of functional conditions during exercise in patients without pronounced deviations in the state of health. The purpose of our study was to compare the indices of immune system and blood circulation in students with different leukogram status in resting state. The study was based on retrospective examinations of CD phenotypes of blood lymphocyte populations, phagocytic and NBT-activity of neutrophils detected by flow cytometry in boys and girls grouped by their physical loads: (1) average mode of motor activity (main group, n = 34), (2) persons involved in athletic exercises (sports group, n = 27), (3) students with low physical fitness (preparatory group, n = 19). The data were grouped according to the program for assessing the type of reaction of the immune system based on leukogram indices in the PROTIST digital information system. 87.5% of those examined in gender-comparable proportions belonged to the three cells of the leukogram matrix: "a reactive type – norm reaction" (45.0% of boys and 42.5% of girls); "immunosuppression – leukopoiesis deficiency" (30.0 and 25.0%, respectively); "activation of adaptive immunity – activation of lymphopoiesis" (17.5% of boys and 15.0% of girls). The ratio of boys and girls included in these cells, depending on the status of their leukogram, is not associated with the level of daily motor activity of examined persons. Subjects with signs of "immunosuppression – leukopoiesis deficiency" exhibited reduced absolute contents of CD3+, CD4+, CD8+ and double-negative CD4-CD8- lymphocytes, phagocytic and NBT-activity of neutrophils, while individuals in the group "activation of adaptive immunity – activation of lymphopoiesis" had a high level of absolute content CD3+, CD4+, CD8+, CD19+ lymphocytes, double-positive CD4+CD8+ and NK cells. Among students from the group "immunosuppression – leukopoiesis insufficiency," systolic blood volume and resting pulse pressure were significantly lower, and the level of diastolic and average dynamic pressure in persons from the group "activation of adaptive immunity – activation of lymphopoiesis" was significantly higher than those in the group "reactive type – norm reaction."
Chronic rhinosinusitis remains a heterogeneous disease with different clinical phenotypes and immunoinflammatory endotypes, which is especially important in case of refractory course after standard drug therapy and/or surgical treatment. Immunohistochemical markers reflecting the predominance of type 1, type 2, and mixed mucosal remodeling are becoming increasingly important for predicting recurrence. The aim of this study is to summarize current data on the diagnostic and prognostic value of immunohistochemical markers in refractory chronic rhinosinusitis with and without nasal polyps, with an emphasis on phenotyping, endotyping, and the association of markers with treatment choice. An analytical review of publications from 2020-2025 from PubMed, PMC, Frontiers and relevant international recommendations has been performed. The selected papers focus on CRSwNP, CRSsNP, tissue eosinophilia, cytokine patterns, markers of remodeling, and predictors of postoperative recurrence. For CRSwNP, the most convincing predictors of recurrence are tissue eosinophilia, periostin, IL-5/IL-13-associated profile, eosinophilic peroxidase, galectin-10/Charcot–Leyden crystals, local IgE, and Bcl2L12. IFNγ/IL-12-, IL-17-, and myeloperoxidase/neutrophil elastase-associated patterns, signs of NET-mediated damage, and fibrous remodeling are more significant for CRSsNP and neutrophilic refractory course variants. The isolated marker is inferior to integral models that include histology, endoscopic assessment, asthma, blood counts, and CT data. Immunohistochemical profiling of the mucous membrane is a promising tool for stratifying the risk of recurrence of refractory chronic rhinosinusitis with and without nasal polyps. The combined assessment of eosinophilic, neutrophilic, and remodeling markers is of the greatest clinical value, allowing for personalized postoperative follow-up, anti-inflammatory therapy, and indications for biologics.
