Background. Peculiarities of the disease and effectiveness of therapy depend on changes in availability and functions of effector immunocompetent cells and cytokine profile. Purpose. To study the peculiarities of immune pathogenetic mechanisms of virus-induced and allergen-induced bronchial asthma phenotypes in children in order to justify the use of immune therapy and to analyze it’s effectiveness. Materials and methods. We have performed an integrated assessment of immunological parameters in 120 children at the age of 3-11 y.o. with virus-induced and allergen-induced phenotypes of bronchial asthma (BA) and in 30 healthy children. Withdrawal criteria: severe BA, immune therapy during preceding 6 months. We used flow flow cytometer COULTER EPICS XL (Beckman Coulter Inc.) for identification of venous blood cells, CYTOKINE-STIMUL-BEST sets (Vektor-Best JSC, Novosibirsk) for levels of spontaneous and mitogen-induced production of cytokines identification. The immunological effectiveness of treatment was analyzed in the open parallel prospective study using random sampling technique in subgroups on the basis of treatment regimen. Statistical data processing was performed by «Statistica 10» program with critical significance level p
The main pathogenetic mechanisms of the SARS-CoV-2 infection include imbalance of immune response and impaired cytokine regulation involving insufficient interferon synthesis at the onset of the disease, and subsequent hyperproduction of proinflammatory cytokines resulting in marked inflammation and damage of pulmonary parenchyma. Our objective was to perform monitoring of cytokine content, determination of antibodies, immune cells, and inflammatory biomarkers in the patients who had coronavirus infection caused by COVID-19, during the disease and over the convalescence period. The study included sixty patients at the age of 18 y.o. and older with severe and moderate course of disease caused by COVID-19. The diagnosis was verified in accordance with provisional instructional guidelines of the Ministry of Healthcare of the Russian Federation “Prevention, diagnosis and treatment of novel coronavirus infection (COVID-19)” version 11 (17.05.2021). The study involved analysis of medical documents, evaluation of differential white blood cell count, T cell subpopulations, C-reactive ptrotein (CRP) levels, interleukin-6 (IL-6), interferon gamma (IFNγ), tumor necrosis factor-alpha (TNFα), as well as IgM and IgG antibodies against SARS-CoV-2.Statistical processing of data was performed by Statistica 13 program with critical significance level p 0.05, correlations were analyzed using Spearman rank correlation coefficient, multidimensional correlation analysis with creation of pleiads, according to V.P. Terentyev’s method (1959), and Shapiro–Wilk testing for normality of data distributions. The sample size made it possible to evaluate the results at a significance of 95-99%. These studies have yielded the results concerning specific changes of the inflammatory biomarkers at different stages of disease, persistent changes in quantitative and qualitative characteristics of immune cells and cytokine levels, correlations between immunological indicators and severity of clinical course, and degree of damage to pulmonary parenchyma. During the period of significant clinical presentations, the patients with severe course of disease exhibited leukopenia with low proportion of lymphocytes, and maintenance of CRP and ESR at high levels for longer terms, including early recovery. Levels and changes in amounts of IgG and IgM antibodies to SАRS-CoV-2 varied in accordance with clinical severity and duration of convalescence period. During the recovery period, an imbalance of regulatory T cell subpopulations and low levels of IFNγ were observed. The stable impairment of structural and functional characteristics of immune cells and aberrant production of cytokines during the disease caused by SARS-CoV-2 may serve as a pre-requisite for monitoring immunological indices in search for personalized immunotropic therapy.
Purpose: to study the changes in quantitative values and functional activity of immunocompetent cells on application of glucoseminylmuramildipeptide in children with allergen-induced phenotype of bronchial asthma.We have performed an integrated assessment of parameters of innate and acquired immunity in 60 children at the age of 3-11 years old with allergen-induced bronchial asthma (BA) with mild clinical course of disease, and in 30 healthy children of the same age. BA phenotypes were verified in accordance with PRACTALL international consensus report (2008). Study exclusion criteria were: severe course of bronchial asthma and application of immunocorrecting therapy during preceding six months. We conducted a prospective parallel open study of the effect of glucoseminylmuramildipeptide on the parameters of immunocompetent cells during three months with division into two control groups by random sampling technique on the basis of therapy being performed. To analyze the venous blood cells, we used flow cytofluorometer COULTER EPICS XL by Beckman Coulter Inc. Cytokine levels were determined using immunoenzyme method with reagents by R&D Diagnostics Inc (USA) and IgE – with reagents by Alkor Bio Company (St. Petersburg), production of cytokines – using reagents by Vektor-Best (Novosibirsk). Statistical processing of data was performed using Statistica 10 program with significance level p < 0.05, assessment of correlations by Spearman correlation analysis, multidimensional correlation analysis with V.P. Terentyev’s method of correlation pleiades (1959) and testing for normal distribution of characteristic values (Shapiro–Wilk). The scope of our study permitted to evaluate its findings with accuracy 95-99%.The changes of the adaptive response system in children with allergen-induced phenotype of BA were characterized by the intensified proliferation, suppression of negative regulation processes, activation of synthesis of Th2-profile cytokines, and intensified synthesis of IgE.The identified impairments of availability, functional activity of immunocompetent cells and cytokine production were preserved in application of inhaled corticosteroids therapy, with further decreasing of IFNγ synthesis.Application of glucoseminylmuramildipeptide in children with BA provided for reduction of spontaneous and mitogen-induced production of IL-4 and correction of deviated structural and functional characteristics of immunocompetent cells.Incorporation of glucoseminylmuramildipeptide into therapeutic regimens for allergen-induced phenotype of BA in children promoted normalization of parameters of the cellular component of immune system, amelioration of Th1/Th2-imbalance, increase of Th1 activity, and adequate spontaneous and induced production of IFNγ by peripheral blood cells.
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