Pub Date : 2024-04-15DOI: 10.15789/1563-0625-eou-2871
M. P. Kostinov, V. Gainitdinova, S. Kazharova, A. E. Vlasenko, V. B. Polishchuk, D. U. Allaberdina
A decrease of nonspecific body resistance, an imbalance of local and systemic immunity and a free-radical oxidation abnormality substantially contribute to the pathogenesis of community-acquired pneumonia (CAP).Purpose: To study the efficiency of including immunomodulators into the comprehensive treatment of nonsevere community-acquired pneumonia and assess the long-term effects of the treatment conducted.Patients (n = 55) with non-severe CAP (41 (31-48) years old, with CRB-65 score of 0.15 (0-1)) are included in the study. Group 1 (control) received only standard CAP therapy; the other two groups received immunomodulators concurrently with the standard therapy: bacterial lysate (BL) for group 2 and azoximer bromide (AzB) for group 3. TNFα and IL-6 concentration was determined on the day of visit, on day 13 and day 60 of follow-up. During 2 years, the incidence of low respiratory tract infections (LRTI) was studied in the same patients with CAP in past (n = 55). All patients (n = 55) had clinical signs of non-severe community-acquired pneumonia. The overall duration of all symptoms was lower in immunomodulators groups as compared to the control group: 12 (11-13) days in BL group (p < 0.001) and 12 (11-12) days in AzB group (p < 0.001) with no statistically significant difference between intervention groups (p = 0.36). During treatment, TNFα and IL-6 concentration decreased on day 13 and day 60 in all patients; in patients who received immunomodulators, TNFα and IL-6 were reliably lower as compared to the control. Changes of TNFα and IL-6 concentration in the groups on day 60 of the study as compared to the baseline showed a decrease in BL group by 85 (-89 – -82) % and 86 (-90 – -85) % (p < 0.001; p = 0.001 and control); in AzB group by 82 (-86 – -80) % and 86 (-88 – -84) % (p = 0.002; p = 0.007 and control). Intensity of IL-6 concentration decrease on day 60 in BL and AzB groups did not differ (p = 0.72). Gender- and age-adjusted odds ratio for the development of low respiratory tract diseases (during 2 years after CAP) in AzB group was 0.15 (0.02-0.93) (p = 0.04) suggesting its protective effect. Inclusion of immunomodulators in basic treatment of non-severe community-acquired pneumonia reduces duration of symptoms and is associated with improvement of the proinflammatory cytokine profile. In 2 years of follow-up, long-term effects of the immunomodulatory therapy showed statistically significant lower incidence of low respiratory tract infections in AzB group only.
{"title":"Experience of using immunomodulatory therapy in the complex treatment of mild community-acquired pneumonia and its long-term results","authors":"M. P. Kostinov, V. Gainitdinova, S. Kazharova, A. E. Vlasenko, V. B. Polishchuk, D. U. Allaberdina","doi":"10.15789/1563-0625-eou-2871","DOIUrl":"https://doi.org/10.15789/1563-0625-eou-2871","url":null,"abstract":"A decrease of nonspecific body resistance, an imbalance of local and systemic immunity and a free-radical oxidation abnormality substantially contribute to the pathogenesis of community-acquired pneumonia (CAP).Purpose: To study the efficiency of including immunomodulators into the comprehensive treatment of nonsevere community-acquired pneumonia and assess the long-term effects of the treatment conducted.Patients (n = 55) with non-severe CAP (41 (31-48) years old, with CRB-65 score of 0.15 (0-1)) are included in the study. Group 1 (control) received only standard CAP therapy; the other two groups received immunomodulators concurrently with the standard therapy: bacterial lysate (BL) for group 2 and azoximer bromide (AzB) for group 3. TNFα and IL-6 concentration was determined on the day of visit, on day 13 and day 60 of follow-up. During 2 years, the incidence of low respiratory tract infections (LRTI) was studied in the same patients with CAP in past (n = 55). All patients (n = 55) had clinical signs of non-severe community-acquired pneumonia. The overall duration of all symptoms was lower in immunomodulators groups as compared to the control group: 12 (11-13) days in BL group (p < 0.001) and 12 (11-12) days in AzB group (p < 0.001) with no statistically significant difference between intervention groups (p = 0.36). During treatment, TNFα and IL-6 concentration decreased on day 13 and day 60 in all patients; in patients who received immunomodulators, TNFα and IL-6 were reliably lower as compared to the control. Changes of TNFα and IL-6 concentration in the groups on day 60 of the study as compared to the baseline showed a decrease in BL group by 85 (-89 – -82) % and 86 (-90 – -85) % (p < 0.001; p = 0.001 and control); in AzB group by 82 (-86 – -80) % and 86 (-88 – -84) % (p = 0.002; p = 0.007 and control). Intensity of IL-6 concentration decrease on day 60 in BL and AzB groups did not differ (p = 0.72). Gender- and age-adjusted odds ratio for the development of low respiratory tract diseases (during 2 years after CAP) in AzB group was 0.15 (0.02-0.93) (p = 0.04) suggesting its protective effect. Inclusion of immunomodulators in basic treatment of non-severe community-acquired pneumonia reduces duration of symptoms and is associated with improvement of the proinflammatory cytokine profile. In 2 years of follow-up, long-term effects of the immunomodulatory therapy showed statistically significant lower incidence of low respiratory tract infections in AzB group only.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"42 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140700384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-asc-2667
I. Goldina, E. V. Markova
Considering the presence of immunomodulatory properties of human endogenous retroviruses, namely (i) the ability to activate the innate immune response by HERVs nucleic acids; (ii) the antigenicity of transcriptionally competent endogenous retroviruses envelope protein molecule, which causes polyclonal activation of lymphocytes; (iii) the absence of HERVs expression and protein production in the thymus during the immune tolerance formation, which allows us to consider these proteins as autoantigens or neoantigens, it seemed relevant to investigate the association of replication-competent human endogenous retrovirus HERV-E λ 4-1 with course of some of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. The aim of this work was a comparative study of the human endogenous retrovirus HERV-E λ 4-1 activation frequency in blood mononuclear cells in multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, as well as in chronic nervous system non-progressive diseases and the degenerative-dystrophic disease of the musculoskeletal system. The peripheral blood mononuclear cells were isolated by the venous blood centrifugation on Ficoll density gradient of 1.078 g/cm3. Expression of the HERV-E λ 4-1 envelope gene was detected by reverse transcriptase polymerase chain reaction. It was found that the HERV-E λ 4-1 envelope gene expression frequency in the chronic non-progressive diseases of nervous system, as well as in degenerative-dystrophic joint disease, is comparable to the expression frequency in conditionally healthy individuals. However, the HERV-E λ 4-1 envelope gene expression frequency in autoimmune diseases significantly exceeded that in conditionally healthy individuals and in non-inflammatory diseases. The maximum values of expression frequency were observed in active multiple sclerosis, significantly higher than in systemic lupus erythematosus and rheumatoid arthritis in the acute stage. Moreover, the expression frequency in the remission stage of multiple sclerosis was significantly lower than in the acute stage of the relapsing-remitted course, as well as in the progredient course. Estimation of HERV-E λ 4-1 envelope gene expression frequency at different severity levels of multiple sclerosis revealed its maximum rates at III and IV-V severity levels, both in relapsing-remitting and progressive course of multiple sclerosis. Thus, activation of the human endogenous retrovirus HERV-E λ 4-1 is associated with the course of autoimmune diseases, namely multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus; it positively correlates with the activity and severity of multiple sclerosis.
{"title":"A comparative study of human endogenous retrovirus HERV-E λ 4-1 activation in autoimmune pathology","authors":"I. Goldina, E. V. Markova","doi":"10.15789/1563-0625-asc-2667","DOIUrl":"https://doi.org/10.15789/1563-0625-asc-2667","url":null,"abstract":"Considering the presence of immunomodulatory properties of human endogenous retroviruses, namely (i) the ability to activate the innate immune response by HERVs nucleic acids; (ii) the antigenicity of transcriptionally competent endogenous retroviruses envelope protein molecule, which causes polyclonal activation of lymphocytes; (iii) the absence of HERVs expression and protein production in the thymus during the immune tolerance formation, which allows us to consider these proteins as autoantigens or neoantigens, it seemed relevant to investigate the association of replication-competent human endogenous retrovirus HERV-E λ 4-1 with course of some of autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus. The aim of this work was a comparative study of the human endogenous retrovirus HERV-E λ 4-1 activation frequency in blood mononuclear cells in multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosus, as well as in chronic nervous system non-progressive diseases and the degenerative-dystrophic disease of the musculoskeletal system. The peripheral blood mononuclear cells were isolated by the venous blood centrifugation on Ficoll density gradient of 1.078 g/cm3. Expression of the HERV-E λ 4-1 envelope gene was detected by reverse transcriptase polymerase chain reaction. It was found that the HERV-E λ 4-1 envelope gene expression frequency in the chronic non-progressive diseases of nervous system, as well as in degenerative-dystrophic joint disease, is comparable to the expression frequency in conditionally healthy individuals. However, the HERV-E λ 4-1 envelope gene expression frequency in autoimmune diseases significantly exceeded that in conditionally healthy individuals and in non-inflammatory diseases. The maximum values of expression frequency were observed in active multiple sclerosis, significantly higher than in systemic lupus erythematosus and rheumatoid arthritis in the acute stage. Moreover, the expression frequency in the remission stage of multiple sclerosis was significantly lower than in the acute stage of the relapsing-remitted course, as well as in the progredient course. Estimation of HERV-E λ 4-1 envelope gene expression frequency at different severity levels of multiple sclerosis revealed its maximum rates at III and IV-V severity levels, both in relapsing-remitting and progressive course of multiple sclerosis. Thus, activation of the human endogenous retrovirus HERV-E λ 4-1 is associated with the course of autoimmune diseases, namely multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematosus; it positively correlates with the activity and severity of multiple sclerosis.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73552931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-fam-2836
I. S. Litvinova, O. Kolenchukova
The Helicobacter pylori bacterium is currently considered one of the leading etiopathogenetic factors in the formation of gastric and duodenal ulcer in children and adults. Despite many studies in this area, the mechanisms of phagocytic activity in response to exposure to Helicobacter pylori are not completely clear. The aim of the work was to obtain results on the functional and metabolic activity of blood neutrophilic granulocytes in children with Helicobacter pylori-associated erosive and ulcerative lesions of the stomach and duodenum. The object of the study are neutrophilic granulocytes isolated from the blood of patients and the control group. Samples were taken from 46 persons with Helicobacter pylori-associated erosive – ulcerative lesions of the stomach and duodenum aged 11 to 18 years and the control group, which consisted of 55 practically healthy persons who had this disease excluded in the same age range. A comparative analysis of the functional activity of cells using chemiluminescent analysis and metabolic activity by the bioluminescent method was carried out. Luminol was used as a chemiluminescence activator. The measurement of the functional activity of phagocytes was based on the determination of the base activity (spontaneous reaction) and the reserve capacity of the cells when they were exposed to the nonspecific inducer zymosan. There is a reduced activation index of neutrophils in patients relative to the control group, which may characterize reduced metabolic reserves of cells. In neutrophilic granulocytes, there is a decrease in G6PDG, an enzyme that triggers glycolysis along the pentose phosphate pathway and contributes to the reduction of nicotinamide adenine dinucleotide phosphate (NADP) to NADPH, which is necessary for the formation of reduced glutathione that binds oxidants. With its insufficiency, a decrease in the energy reserves of cells occurs. In neutrophilic blood granulocytes in children with erosive and ulcerative lesions of the stomach and duodenum with H. pylori infection, a decrease in metabolic reserves is observed, which is associated with inhibition of metabolic processes in cells.
{"title":"Functional and metabolic activity of blood neutrophilic granulocytes in children with erosive and ulcerative lesions of the stomach and duodenum with detected Helicobacter pylori infection","authors":"I. S. Litvinova, O. Kolenchukova","doi":"10.15789/1563-0625-fam-2836","DOIUrl":"https://doi.org/10.15789/1563-0625-fam-2836","url":null,"abstract":"The Helicobacter pylori bacterium is currently considered one of the leading etiopathogenetic factors in the formation of gastric and duodenal ulcer in children and adults. Despite many studies in this area, the mechanisms of phagocytic activity in response to exposure to Helicobacter pylori are not completely clear. The aim of the work was to obtain results on the functional and metabolic activity of blood neutrophilic granulocytes in children with Helicobacter pylori-associated erosive and ulcerative lesions of the stomach and duodenum. The object of the study are neutrophilic granulocytes isolated from the blood of patients and the control group. Samples were taken from 46 persons with Helicobacter pylori-associated erosive – ulcerative lesions of the stomach and duodenum aged 11 to 18 years and the control group, which consisted of 55 practically healthy persons who had this disease excluded in the same age range. A comparative analysis of the functional activity of cells using chemiluminescent analysis and metabolic activity by the bioluminescent method was carried out. Luminol was used as a chemiluminescence activator. The measurement of the functional activity of phagocytes was based on the determination of the base activity (spontaneous reaction) and the reserve capacity of the cells when they were exposed to the nonspecific inducer zymosan. There is a reduced activation index of neutrophils in patients relative to the control group, which may characterize reduced metabolic reserves of cells. In neutrophilic granulocytes, there is a decrease in G6PDG, an enzyme that triggers glycolysis along the pentose phosphate pathway and contributes to the reduction of nicotinamide adenine dinucleotide phosphate (NADP) to NADPH, which is necessary for the formation of reduced glutathione that binds oxidants. With its insufficiency, a decrease in the energy reserves of cells occurs. In neutrophilic blood granulocytes in children with erosive and ulcerative lesions of the stomach and duodenum with H. pylori infection, a decrease in metabolic reserves is observed, which is associated with inhibition of metabolic processes in cells.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"85 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72754784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-cat-2750
M. Nikolenko, N. Baryshnikova, O. I. Malishevskaya, E. M. Vaseva
Rythmometric markers can be identified within a day during the study of biological characteristics in order to be used for differential diagnostics of pathogens of different patients’ physical condition. These principles are based on analysis of clinical isolates С. albicans, С. tropicalis and C. krusei allocated from the vaginal microbiota at Candida dysbiosis condition. Control examples were the master samples from the American Type Culture Collection (ATCC). Detailed research was conducted on physiological characteristics through the formation of biofilms by yeast pathogens. Biological activity of Candida sp. biofilming was observed within 2 days with 4 hours interval in winter. Daily cultures were used for the experiment to correspond to their maximum adhesion to the glass surface. It was important to obtain 6 measurements per day with 3-5 times repetition of experiment conditions during the specified timeline. In order to determine the periodicity of the parameters studied, the data was statistically processed by Student’s t-test, using Mann–Whitney criteria and nonparametric method of least square method.It was found out that biofilming activity during 24 hours (р < 0.05) of fungi exists and that all species have many principles in common. It was attested that the main rhythmometric parameters of diagnostic significance are the rhythm period and amplitude-phase stability. It was found that the daily dynamics of C. albicans 24433 biofilm formation from American Type Culture Collection was characterized by an ultradian (about 12-hours) contribution of the rhythm in the morning – 4 A.M and in the evening – 4 P.M. Significant circadian (approx. daily) rhythms of adhesion glass surface activity were revealed in C. non-albicans from American Type Culture Collection. The dynamic of biofilm formation isolates of yeast from female reproductive organs with Candida pathology was characterized by reliable ultradian (about 12-hour) harmonics which biological significance defines resistance to external impact and the ability to adaptively respond to periodic stimuli.To sum up, implementation of the chronobiological approach has opened up new prospects for studying the physiology of Сandida sp., as it enables us to predict the dynamics of microbial states and takes into account the specificity of emergency and long-term adaptation to different environmental factors. The detection of the circadian rhythm of biofilm formation activity of different Candida sp. strains provides the possibility to manage the vitality of the Society of Bacteria and Fungi and predicts its resistance to various antibiotics.
{"title":"Chronobiological approach to study the physiological activity of Candida species","authors":"M. Nikolenko, N. Baryshnikova, O. I. Malishevskaya, E. M. Vaseva","doi":"10.15789/1563-0625-cat-2750","DOIUrl":"https://doi.org/10.15789/1563-0625-cat-2750","url":null,"abstract":"Rythmometric markers can be identified within a day during the study of biological characteristics in order to be used for differential diagnostics of pathogens of different patients’ physical condition. These principles are based on analysis of clinical isolates С. albicans, С. tropicalis and C. krusei allocated from the vaginal microbiota at Candida dysbiosis condition. Control examples were the master samples from the American Type Culture Collection (ATCC). Detailed research was conducted on physiological characteristics through the formation of biofilms by yeast pathogens. Biological activity of Candida sp. biofilming was observed within 2 days with 4 hours interval in winter. Daily cultures were used for the experiment to correspond to their maximum adhesion to the glass surface. It was important to obtain 6 measurements per day with 3-5 times repetition of experiment conditions during the specified timeline. In order to determine the periodicity of the parameters studied, the data was statistically processed by Student’s t-test, using Mann–Whitney criteria and nonparametric method of least square method.It was found out that biofilming activity during 24 hours (р < 0.05) of fungi exists and that all species have many principles in common. It was attested that the main rhythmometric parameters of diagnostic significance are the rhythm period and amplitude-phase stability. It was found that the daily dynamics of C. albicans 24433 biofilm formation from American Type Culture Collection was characterized by an ultradian (about 12-hours) contribution of the rhythm in the morning – 4 A.M and in the evening – 4 P.M. Significant circadian (approx. daily) rhythms of adhesion glass surface activity were revealed in C. non-albicans from American Type Culture Collection. The dynamic of biofilm formation isolates of yeast from female reproductive organs with Candida pathology was characterized by reliable ultradian (about 12-hour) harmonics which biological significance defines resistance to external impact and the ability to adaptively respond to periodic stimuli.To sum up, implementation of the chronobiological approach has opened up new prospects for studying the physiology of Сandida sp., as it enables us to predict the dynamics of microbial states and takes into account the specificity of emergency and long-term adaptation to different environmental factors. The detection of the circadian rhythm of biofilm formation activity of different Candida sp. strains provides the possibility to manage the vitality of the Society of Bacteria and Fungi and predicts its resistance to various antibiotics.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73094068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-ici-2827
T. Yurakova, E. Gorshkova, M. A. Nosenko, E. Gubernatorova, M. Drutskaya
To date, much remains unclear about the pathogenesis of asthma, one of the most common chronic and highly heterogenic diseases of the respiratory system. The lack of specific and highly effective therapy in case of certain asthma subtypes requires the search for new approaches to treatment. One possible approach would be to influence the metabolism and immune functions of myeloid cells. This approach finds its application in the treatment of cancer and other diseases in the pathogenesis of which macrophages play an important role. It was shown that the pathogenesis of allergic asthma in response to one of the most common allergens, house dust mite, is due to a metabolic TNF-mediated reprogramming of alveolar macrophages. This suggests that influencing the process of TNF production or metabolic adaptations with specific blockers may also lead to a reduction in the symptoms of the course of the disease as a whole. In this work, we experimentally tested whether the previously obtained phenotype that occurs in macrophages in response to HDM cultured in DMEM is preserved if cells are cultured under more physiologically relevant conditions: in a medium closely related in composition to blood plasma. We also analyzed open databases of alveolar macrophages sequencing obtained from patients with asthma or from the lungs of mice in an HDM-induced asthma model in order to correlate specific immunometabolic changes. It was found that macrophages cultured under conditions close to physiological, simultaneously increase the rates of respiration and glycolysis, and also produce TNF in response to HDM. The observed phenotype is consistent with transcriptomic analyzes performed on human and mouse samples, which revealed an increase in the expression of genes related to glycolysis, oxidative phosphorylation, and the TNF signaling pathway. Thus, the data confirm the relevance of the phenotype obtained in vitro to the changes occurring in the in vivo system. However, functional verification at the level of metabolites, proteins and changes in metabolic activity is also required. In addition, it remains to be established how the blocking of individual metabolic pathways affects the features of the functional macrophage phenotype that occurs in response to HDM, and whether this effect can alleviate asthma symptoms.
{"title":"Immunometabolic changes in macrophages in response to house dust mite extract","authors":"T. Yurakova, E. Gorshkova, M. A. Nosenko, E. Gubernatorova, M. Drutskaya","doi":"10.15789/1563-0625-ici-2827","DOIUrl":"https://doi.org/10.15789/1563-0625-ici-2827","url":null,"abstract":"To date, much remains unclear about the pathogenesis of asthma, one of the most common chronic and highly heterogenic diseases of the respiratory system. The lack of specific and highly effective therapy in case of certain asthma subtypes requires the search for new approaches to treatment. One possible approach would be to influence the metabolism and immune functions of myeloid cells. This approach finds its application in the treatment of cancer and other diseases in the pathogenesis of which macrophages play an important role. It was shown that the pathogenesis of allergic asthma in response to one of the most common allergens, house dust mite, is due to a metabolic TNF-mediated reprogramming of alveolar macrophages. This suggests that influencing the process of TNF production or metabolic adaptations with specific blockers may also lead to a reduction in the symptoms of the course of the disease as a whole. In this work, we experimentally tested whether the previously obtained phenotype that occurs in macrophages in response to HDM cultured in DMEM is preserved if cells are cultured under more physiologically relevant conditions: in a medium closely related in composition to blood plasma. We also analyzed open databases of alveolar macrophages sequencing obtained from patients with asthma or from the lungs of mice in an HDM-induced asthma model in order to correlate specific immunometabolic changes. It was found that macrophages cultured under conditions close to physiological, simultaneously increase the rates of respiration and glycolysis, and also produce TNF in response to HDM. The observed phenotype is consistent with transcriptomic analyzes performed on human and mouse samples, which revealed an increase in the expression of genes related to glycolysis, oxidative phosphorylation, and the TNF signaling pathway. Thus, the data confirm the relevance of the phenotype obtained in vitro to the changes occurring in the in vivo system. However, functional verification at the level of metabolites, proteins and changes in metabolic activity is also required. In addition, it remains to be established how the blocking of individual metabolic pathways affects the features of the functional macrophage phenotype that occurs in response to HDM, and whether this effect can alleviate asthma symptoms.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75584752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-iif-2766
E. Bystritskaia, N. Murashkin, O. Olisova, A. I. Materikin, M. Potapova, A. Vinnitskaya, A. G. Upatova
Atopic dermatitis is a multifactorial genetically determined inflammatory skin disease characterized by itching, chronically relapsing dermatitis, age-related features of localization and morphology of lesions. The pathogenesis of atopic dermatitis is complex and includes epigenetic alterations, involved in the genomic adaptation, immune response reactions and dysfunction of the epithelial barrier that together trigger the development of atopic dermatitis. The aim of this study is to detect the expression level for IL4, IL13, IL33, TLR2, TLR9 genes in the biological materials of atopic patients.The targeted genes for further expression evaluation were selected according to our previous findings on genome-wide methylation study. We detected the cascades with the differentially methylated genes that are most likely to take place in atopic dermatitis. Thus, we investigated expression levels for the IL4, IL13, IL33, TLR2, TLR9 genes in the skin, peripheral blood mononuclear cells and whole blood cells using RT-PCR on 55 pediatric patients and 26 healthy volunteers, and on 50 adult patients. Statistical analysis was performed with the use of Kruskal-Wallis H test and Mann-Whitney U test. Targeted expression analysis revealed that in the skin samples the expression of TLR9 and IL4 was 12 times significantly lower (p < 0.0001, p < 0.0005) in the lesional skin; and there was a 6-fold decrease in case of TLR2 (p < 0.01). The results for blood mononuclear cells differed and expression levels for most of the assessed targets were significantly higher before treatment. We have also found out that those differences were strongly pronounced especially in an elder age group (12-18 y.o.). Studying the IL33 gene expression in the whole blood samples of adults revealed that its level was significantly higher in case of patients with moderate form of AD. Besides, we concluded that locally in the affected skin inflammatory immune response may dominate; in the mononuclear cells Th2 immune response apparently takes place. New insights on immunological markers and links among them may shed a light on atopic dermatitis pathogenic mechanisms. The detected molecules could play role as potential therapeutic targets and form a management approach for patients with atopic dermatitis.
{"title":"Innate immune factor gene expression profiles in patients with atopic dermatitis","authors":"E. Bystritskaia, N. Murashkin, O. Olisova, A. I. Materikin, M. Potapova, A. Vinnitskaya, A. G. Upatova","doi":"10.15789/1563-0625-iif-2766","DOIUrl":"https://doi.org/10.15789/1563-0625-iif-2766","url":null,"abstract":"Atopic dermatitis is a multifactorial genetically determined inflammatory skin disease characterized by itching, chronically relapsing dermatitis, age-related features of localization and morphology of lesions. The pathogenesis of atopic dermatitis is complex and includes epigenetic alterations, involved in the genomic adaptation, immune response reactions and dysfunction of the epithelial barrier that together trigger the development of atopic dermatitis. The aim of this study is to detect the expression level for IL4, IL13, IL33, TLR2, TLR9 genes in the biological materials of atopic patients.The targeted genes for further expression evaluation were selected according to our previous findings on genome-wide methylation study. We detected the cascades with the differentially methylated genes that are most likely to take place in atopic dermatitis. Thus, we investigated expression levels for the IL4, IL13, IL33, TLR2, TLR9 genes in the skin, peripheral blood mononuclear cells and whole blood cells using RT-PCR on 55 pediatric patients and 26 healthy volunteers, and on 50 adult patients. Statistical analysis was performed with the use of Kruskal-Wallis H test and Mann-Whitney U test. Targeted expression analysis revealed that in the skin samples the expression of TLR9 and IL4 was 12 times significantly lower (p < 0.0001, p < 0.0005) in the lesional skin; and there was a 6-fold decrease in case of TLR2 (p < 0.01). The results for blood mononuclear cells differed and expression levels for most of the assessed targets were significantly higher before treatment. We have also found out that those differences were strongly pronounced especially in an elder age group (12-18 y.o.). Studying the IL33 gene expression in the whole blood samples of adults revealed that its level was significantly higher in case of patients with moderate form of AD. Besides, we concluded that locally in the affected skin inflammatory immune response may dominate; in the mononuclear cells Th2 immune response apparently takes place. New insights on immunological markers and links among them may shed a light on atopic dermatitis pathogenic mechanisms. The detected molecules could play role as potential therapeutic targets and form a management approach for patients with atopic dermatitis.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81797153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-ieo-2816
Yulia S. Torshina, N. Serebryanaya, T. Glazanova, M. A. Mikhalyova, S. Voloshin
Bruton's tyrosine kinase (BTK) inhibitors represent a class of drugs that have demonstrated their efficacy and safety in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphomas who were considered refractory to any previously used type of therapy. BTK plays a key role in all stages of B lymphocyte development, but in recent years, there have been data indicating that BTK is also involved in the activation of myeloid cells.The aim of this study is to analyze and systematize all published materials on the immunomodulatory effects of BTK inhibitors (ibrutinib, acalabrutinib, etc.).A systematic review of the scientific literature was performed using a step-by-step search process in electronic databases (PubMed, Web of Science, ScienceDirect, and Scopus). The following keywords were used in the database search: “CLL”, “BTK”, “ibrutinib”, “COVID-19”, “allergy”, “inflammation.” The search for studies was conducted from the time of the first BTK inhibitor drug (ibrutinib) appearance in 2009 until December 2022.The results of the study on the influence of BTK inhibitors on the functional state of B and T lymphocytes, neutrophils, and monocytes/macrophages are presented. The immunomodulatory effects of ibrutinib on adaptive and innate immune system cells, including CD4+ and CD8+T lymphocytes and NK cells, are described. Since BTK inhibitors alter the functional activity of phagocytic cells and the ratio of T cell populations, there is a suggestion about the possibility of using these drugs for the treatment of other nosological forms, not only B cell malignancies, which is currently being studied in clinical trials. Data on the use of BTK inhibitors to combat hyperacute inflammation and to suppress allergic reactions, including anaphylaxis, are summarized. In addition, the expediency of short-term use of BTK inhibitors to reduce the risk of side effects during oral immunotherapy and for desensitization to drugs is discussed.The presented data indicate that BTK inhibitors are promising drugs with immunomodulatory effects. However, BTK inhibitors need to increase selectivity to reduce off-target effects on other kinases.
布鲁顿酪氨酸激酶(BTK)抑制剂代表了一类药物，已证明其对慢性淋巴细胞白血病和非霍奇金淋巴瘤患者的有效性和安全性，这些患者被认为对任何先前使用的治疗类型都是难治性的。BTK在B淋巴细胞发育的各个阶段都起着关键作用，但近年来，有数据表明BTK也参与骨髓细胞的活化。本研究的目的是对BTK抑制剂(ibrutinib, acalabrutinib等)免疫调节作用的所有已发表的资料进行分析和系统化。通过电子数据库(PubMed、Web of Science、ScienceDirect和Scopus)的逐步搜索过程，对科学文献进行了系统的综述。在数据库搜索中使用了以下关键词:“CLL”、“BTK”、“ibrutinib”、“COVID-19”、“过敏”、“炎症”。从2009年第一个BTK抑制剂药物(ibrutinib)出现到2022年12月，研究的搜索一直在进行。给出了BTK抑制剂对B淋巴细胞、T淋巴细胞、中性粒细胞、单核/巨噬细胞功能状态影响的研究结果。描述了伊鲁替尼对适应性和先天免疫系统细胞的免疫调节作用，包括CD4+和CD8+T淋巴细胞和NK细胞。由于BTK抑制剂改变吞噬细胞的功能活性和T细胞群的比例，因此有可能使用这些药物治疗其他疾病形式，而不仅仅是B细胞恶性肿瘤，目前正在临床试验中进行研究。总结了使用BTK抑制剂对抗超急性炎症和抑制过敏反应(包括过敏反应)的数据。此外，还讨论了短期使用BTK抑制剂以减少口服免疫治疗期间副作用的风险和对药物脱敏的便捷性。这些数据表明，BTK抑制剂是一种有前景的具有免疫调节作用的药物。然而，BTK抑制剂需要增加选择性以减少对其他激酶的脱靶效应。
{"title":"Immunomodulating effects of antitumor drugs Bruton tyrosine kinase inhibitors and the possibility of their use in allergic and infectious diseases","authors":"Yulia S. Torshina, N. Serebryanaya, T. Glazanova, M. A. Mikhalyova, S. Voloshin","doi":"10.15789/1563-0625-ieo-2816","DOIUrl":"https://doi.org/10.15789/1563-0625-ieo-2816","url":null,"abstract":"Bruton's tyrosine kinase (BTK) inhibitors represent a class of drugs that have demonstrated their efficacy and safety in patients with chronic lymphocytic leukemia and non-Hodgkin's lymphomas who were considered refractory to any previously used type of therapy. BTK plays a key role in all stages of B lymphocyte development, but in recent years, there have been data indicating that BTK is also involved in the activation of myeloid cells.The aim of this study is to analyze and systematize all published materials on the immunomodulatory effects of BTK inhibitors (ibrutinib, acalabrutinib, etc.).A systematic review of the scientific literature was performed using a step-by-step search process in electronic databases (PubMed, Web of Science, ScienceDirect, and Scopus). The following keywords were used in the database search: “CLL”, “BTK”, “ibrutinib”, “COVID-19”, “allergy”, “inflammation.” The search for studies was conducted from the time of the first BTK inhibitor drug (ibrutinib) appearance in 2009 until December 2022.The results of the study on the influence of BTK inhibitors on the functional state of B and T lymphocytes, neutrophils, and monocytes/macrophages are presented. The immunomodulatory effects of ibrutinib on adaptive and innate immune system cells, including CD4+ and CD8+T lymphocytes and NK cells, are described. Since BTK inhibitors alter the functional activity of phagocytic cells and the ratio of T cell populations, there is a suggestion about the possibility of using these drugs for the treatment of other nosological forms, not only B cell malignancies, which is currently being studied in clinical trials. Data on the use of BTK inhibitors to combat hyperacute inflammation and to suppress allergic reactions, including anaphylaxis, are summarized. In addition, the expediency of short-term use of BTK inhibitors to reduce the risk of side effects during oral immunotherapy and for desensitization to drugs is discussed.The presented data indicate that BTK inhibitors are promising drugs with immunomodulatory effects. However, BTK inhibitors need to increase selectivity to reduce off-target effects on other kinases.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85039633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-iot-2712
N. Chepurnova, O. N. Birko, S. Knysh, A. Rudneva, V. V. Zharskaya, A. Peskova, R. B. Mamedov
Numerous studies show the role of the cytokine network in the pathogenesis of anxiety and depression. However, at present, studies of the correlation between the levels of pro-inflammatory and antiinflammatory cytokines and the level of emotional stress are rather few. The aim of the study was to analyze the serum levels of pro-inflammatory and anti-inflammatory cytokines and the emotional state in apparently healthy women depending on age. Serum levels were tested IL-1β, IL-6, IL-17, IFNγ, IL-10 and IL-4 in 100 apparently healthy women, who were divided into 3 groups depending on age (WHO): 18-44 (young age) 30 people, 45-59 (middle age) 40 people, 60-74 (old age) 30 people (sandwich variant of enzyme-linked immunosorbent assay, pg/mL). To assess the emotional component of health, all the subjects passed the questionnaire SF-36 “Assessment of the quality of life”. Statistical processing of the obtained data was carried out using the analytical software IBM SPSS Statistics, 22.0. In practically healthy women, an increase in the values of IL-1β and IL-6 was found in the elderly group (p < 0.05), while no differences were found between the groups of young and middle age. The level of IFNγ in all age groups of women did not differ significantly. At the same time, in the elderly group, the levels of IFNγ in 40% ranged from 1.04 to 8.76 pg/mL, and in 60% of women – from 24.85 to 28.5 pg/mL. IL-17 was also high (p < 0.05-0.01) in the group of women aged 60-74. In the anti-inflammatory link, the opposite picture was observed, for example, in young and middle-aged women, the levels of IL-10 and IL-4 were higher than in the elderly group. Thus, the analysis made it possible to state that the parameters of the cytokine profile and emotional state in women are associated with age.
{"title":"Indicators of the cytokine system in practically healthy women of different ages and interrelation with the emotional state","authors":"N. Chepurnova, O. N. Birko, S. Knysh, A. Rudneva, V. V. Zharskaya, A. Peskova, R. B. Mamedov","doi":"10.15789/1563-0625-iot-2712","DOIUrl":"https://doi.org/10.15789/1563-0625-iot-2712","url":null,"abstract":"Numerous studies show the role of the cytokine network in the pathogenesis of anxiety and depression. However, at present, studies of the correlation between the levels of pro-inflammatory and antiinflammatory cytokines and the level of emotional stress are rather few. The aim of the study was to analyze the serum levels of pro-inflammatory and anti-inflammatory cytokines and the emotional state in apparently healthy women depending on age. Serum levels were tested IL-1β, IL-6, IL-17, IFNγ, IL-10 and IL-4 in 100 apparently healthy women, who were divided into 3 groups depending on age (WHO): 18-44 (young age) 30 people, 45-59 (middle age) 40 people, 60-74 (old age) 30 people (sandwich variant of enzyme-linked immunosorbent assay, pg/mL). To assess the emotional component of health, all the subjects passed the questionnaire SF-36 “Assessment of the quality of life”. Statistical processing of the obtained data was carried out using the analytical software IBM SPSS Statistics, 22.0. In practically healthy women, an increase in the values of IL-1β and IL-6 was found in the elderly group (p < 0.05), while no differences were found between the groups of young and middle age. The level of IFNγ in all age groups of women did not differ significantly. At the same time, in the elderly group, the levels of IFNγ in 40% ranged from 1.04 to 8.76 pg/mL, and in 60% of women – from 24.85 to 28.5 pg/mL. IL-17 was also high (p < 0.05-0.01) in the group of women aged 60-74. In the anti-inflammatory link, the opposite picture was observed, for example, in young and middle-aged women, the levels of IL-10 and IL-4 were higher than in the elderly group. Thus, the analysis made it possible to state that the parameters of the cytokine profile and emotional state in women are associated with age.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"211 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77051323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-faf-2713
A. A. Maksimova, L. Sakhno, A. Ostanin
Macrophages are involved in the regulation of fibrogenesis and turnover of the extracellular matrix. One way to perform this function is through the production of profibrotic and fibrolytic factors including fibronectin, laminin, collagen, and extracellular matrix proteases. The production of most of them has been well studied in experimental models; however, much remains unclear regarding human macrophages. Therefore, the aim of this study was to study the content of extracellular matrix proteases (MMP-2 and MMP-9, cathepsin L), their inhibitors (TIMP-1), and collagen (type I) in supernatants of differently activated human macrophages. We compared macrophages differentiated by M-CSF or GM-CSF and further polarized in M1 with lipopolysaccharide, in M2a with IL-4, and in M2c with dexamethasone. Macrophages was obtained from peripheral blood monocytes. The content of MMPs, TIMP, cathepsin, and collagen was determined using appropriate ELISA kits. The results obtained demonstrate that differentiation factors are more important for the production of the above factors compared to polarizing stimuli (lipopolysaccharide, IL-4, dexamethasone). Moreover, macrophages differentiated by M-CSF showed predominantly antifibrotic activity because of pronounced MMPs production, while GM-CSF-induced cultures, on the contrary, were characterized by profibrotic properties due to the high level of TIMP-1 and type I collagen. M1, M2a, and M2c, induced by M-CSF, differed only in MMP-2 production, and M2a produced this metalloproteinase more than other subtypes. In the case of GM-CSF-differentiated cells, a higher level of production of TIMP-1 and, to a lesser extent, type I collagen was characteristic of M1, whereas M2c have minimal concentration of them among GM-CSF-induced macrophage subtypes. Concerning the level of cathepsin L production was relatively constant and did not depend on the generation conditions (differentiation and polarizing signals). Thus, the data obtained help to identify macrophage subtypes with anti- or profibrotic potential and may be useful for the development of cell therapy for diseases associated with fibrogenesis dysregulation.
{"title":"Fibrogenic and fibrolytic potential of differently activated human macrophages","authors":"A. A. Maksimova, L. Sakhno, A. Ostanin","doi":"10.15789/1563-0625-faf-2713","DOIUrl":"https://doi.org/10.15789/1563-0625-faf-2713","url":null,"abstract":"Macrophages are involved in the regulation of fibrogenesis and turnover of the extracellular matrix. One way to perform this function is through the production of profibrotic and fibrolytic factors including fibronectin, laminin, collagen, and extracellular matrix proteases. The production of most of them has been well studied in experimental models; however, much remains unclear regarding human macrophages. Therefore, the aim of this study was to study the content of extracellular matrix proteases (MMP-2 and MMP-9, cathepsin L), their inhibitors (TIMP-1), and collagen (type I) in supernatants of differently activated human macrophages. We compared macrophages differentiated by M-CSF or GM-CSF and further polarized in M1 with lipopolysaccharide, in M2a with IL-4, and in M2c with dexamethasone. Macrophages was obtained from peripheral blood monocytes. The content of MMPs, TIMP, cathepsin, and collagen was determined using appropriate ELISA kits. The results obtained demonstrate that differentiation factors are more important for the production of the above factors compared to polarizing stimuli (lipopolysaccharide, IL-4, dexamethasone). Moreover, macrophages differentiated by M-CSF showed predominantly antifibrotic activity because of pronounced MMPs production, while GM-CSF-induced cultures, on the contrary, were characterized by profibrotic properties due to the high level of TIMP-1 and type I collagen. M1, M2a, and M2c, induced by M-CSF, differed only in MMP-2 production, and M2a produced this metalloproteinase more than other subtypes. In the case of GM-CSF-differentiated cells, a higher level of production of TIMP-1 and, to a lesser extent, type I collagen was characteristic of M1, whereas M2c have minimal concentration of them among GM-CSF-induced macrophage subtypes. Concerning the level of cathepsin L production was relatively constant and did not depend on the generation conditions (differentiation and polarizing signals). Thus, the data obtained help to identify macrophage subtypes with anti- or profibrotic potential and may be useful for the development of cell therapy for diseases associated with fibrogenesis dysregulation.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"41 7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85384457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-01DOI: 10.15789/1563-0625-ntf-2799
O. Kurbatova, S. Petrichuk, D. Kuptsova, G. Movsisyan, T. Radygina, A. Komarova, A. Anushenko, E. Freidlin, E. Semikina, A. Potapov, A. Fisenko
Wilson's disease (WD) is a rare hereditary disease caused by a deficiency of the ATF7B transporter. The accumulation of copper can cause damage to organs and cells, mainly the liver. Copper exposure can modulate cytokine synthesis through molecular and cellular signaling pathways, including the nuclear transcription factor NF-kB pathway. NF-kB is the main regulator of inflammation and cell death, acts as a central link between liver damage, fibrosis and hepatocellular carcinoma. An excess of NF-kB-dependent cytokine response stimulates inflammatory reactions, but excessive inhibition of NF-kB can negatively affect the viability of hepatocytes. Method of flow cytometry with visualization — Amnis ImageStreamX allows to evaluate the activity of NF-kB (% of activated cells in cell populations). The aim: to evaluate the activity of NF-kB in lymphocyte populations in children with WD disease. Immunophenotyping of lymphocytes and assessment of the level of translocation of NF-kB were performed in 52 children with WD and in 25 children of comparison group. The mass concentration of copper in daily urine was determined by atomic absorption method using the AAnalyst 800 spectrometer. In children with WD, the content of cells with NF-kB translocation varied from 5 to 90% depending on the lymphocyte population; the highest level was detected in B cells — 57.5 (37-68) %. A significant difference in distributions of the number of cells with NF-kB translocation between WD and healthy children was shown (F-criterion, p < 0.01). In most cases, children with WD are characterized by a decrease in the activity of NF-kB in populations of B cells (in 43% of cases), T helper cells (48%), T cytotoxic (44%) and Th17 lymphocytes (41%). In children with WD, the concentration of copper varied from 9.7 to 2582 mcg/day, Me = 616 (210-1173). A direct relationship was obtained between the copper content in urine and the level of translocation of NF-kB in B lymphocytes, r = 0.34, p = 0.016. The activity of the NF-kB correlates with biochemical markers of the severity of liver damage (ALT, AST, GGT) and with copper content in urine. The study of the NF-kB signaling pathway seems promising for a better understanding of the pathogenetic mechanisms of the formation of inflammation and liver fibrosis in children with WD.
{"title":"Nuclear transcription factor kB (NF-kB) activity in lymphocyte populations in children with Wilson-Konovalov disease","authors":"O. Kurbatova, S. Petrichuk, D. Kuptsova, G. Movsisyan, T. Radygina, A. Komarova, A. Anushenko, E. Freidlin, E. Semikina, A. Potapov, A. Fisenko","doi":"10.15789/1563-0625-ntf-2799","DOIUrl":"https://doi.org/10.15789/1563-0625-ntf-2799","url":null,"abstract":"Wilson's disease (WD) is a rare hereditary disease caused by a deficiency of the ATF7B transporter. The accumulation of copper can cause damage to organs and cells, mainly the liver. Copper exposure can modulate cytokine synthesis through molecular and cellular signaling pathways, including the nuclear transcription factor NF-kB pathway. NF-kB is the main regulator of inflammation and cell death, acts as a central link between liver damage, fibrosis and hepatocellular carcinoma. An excess of NF-kB-dependent cytokine response stimulates inflammatory reactions, but excessive inhibition of NF-kB can negatively affect the viability of hepatocytes. Method of flow cytometry with visualization — Amnis ImageStreamX allows to evaluate the activity of NF-kB (% of activated cells in cell populations). The aim: to evaluate the activity of NF-kB in lymphocyte populations in children with WD disease. Immunophenotyping of lymphocytes and assessment of the level of translocation of NF-kB were performed in 52 children with WD and in 25 children of comparison group. The mass concentration of copper in daily urine was determined by atomic absorption method using the AAnalyst 800 spectrometer. In children with WD, the content of cells with NF-kB translocation varied from 5 to 90% depending on the lymphocyte population; the highest level was detected in B cells — 57.5 (37-68) %. A significant difference in distributions of the number of cells with NF-kB translocation between WD and healthy children was shown (F-criterion, p < 0.01). In most cases, children with WD are characterized by a decrease in the activity of NF-kB in populations of B cells (in 43% of cases), T helper cells (48%), T cytotoxic (44%) and Th17 lymphocytes (41%). In children with WD, the concentration of copper varied from 9.7 to 2582 mcg/day, Me = 616 (210-1173). A direct relationship was obtained between the copper content in urine and the level of translocation of NF-kB in B lymphocytes, r = 0.34, p = 0.016. The activity of the NF-kB correlates with biochemical markers of the severity of liver damage (ALT, AST, GGT) and with copper content in urine. The study of the NF-kB signaling pathway seems promising for a better understanding of the pathogenetic mechanisms of the formation of inflammation and liver fibrosis in children with WD.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"10 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78294551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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