Pub Date : 2023-06-01DOI: 10.15789/1563-0625-pit-2867
A. Popova, V. S. Smirnov, S. Egorova, I. Drozd, A. M. Milichkina, A. M. Dashkevich, Z. Nurmatov, G. Melik-Andreasyan, M. Ruziev, A. Totolian
The ongoing coronavirus disease (COVID-19) pandemic over the past three years has caused close attention to the problem of herd immunity, which is understood as: "resistance to the spread of a contagious disease within a population or herd". Collective immunity is formed both as a result of infection (natural spread of the pathogen in a population of susceptible individuals) and as a result of the use of specific vaccines. During the COVID-19 pandemic, both mechanisms for the formation of collective immunity were realized. In the first wave, there was a natural formation of collective immunity to the virus following recoveries from COVID-19 caused by pandemic spread of SARS-CoV-2. Starting from December 2020, the widespread use of specific vaccines against SARS-CoV-2 began in the USA, Great Britain, China, Russia, and a number of other countries. This launched the process of post-vaccination collective immunity formation; its features have depended on the vaccine types implemented. Currently, in those countries where vaccination and revaccination of recovered patients is widely carried out, immunity is "hybrid" in nature. Several commonalities should be noted in the pandemic experience: a somewhat regular, periodic (wavelike) nature of the COVID-19 epidemic process; changes in pathogen genetics in variants in all countries; and expansive mass vaccination programs in many populations. From these, we can draw some conclusions about the general trend for all countries in the formation of collective immunity during the pandemic: At the beginning of the pandemic in 2020, overall population seroprevalence did not exceed 20%. Other findings were: the highest seroprevalence rates were noted in the children's age group; pronounced regional differences were revealed; and the highest indicators were noted among medical workers. Collective immunity developed as a result of infection or illness, and in the majority of seropositive volunteers, it was represented by antibodies to both antigens. At the height of the pandemic in the summer of 2021, population seroprevalence reached 50%. This was due to both a significant number of convalescents and the start of mass vaccination campaigns. In all countries, specific differences in seroprevalence (by age, region, profession) leveled out, leading to more uniformity. During this period, the formation of "hybrid" immunity is clearly prominent, and the proportion of individuals with antibodies to RBD alone increased (due to vaccination with vector vaccines). Later, mass vaccination, as well as involvement of most of the population in the epidemic process due to the emergence of the highly contagious Omicron strain, raised the level of collective immunity to 80-90%. This led to a sharp decrease in COVID-19 incidence in the second half of 2022 in all countries participating in the study. In the later stages of the pandemic (2022-2023), almost 90% of seropositive volunteers had hybrid immunity, reflected as antibodies to
{"title":"Patterns in the development of collective immunity to SARS-CoV-2 during the COVID-19 pandemic","authors":"A. Popova, V. S. Smirnov, S. Egorova, I. Drozd, A. M. Milichkina, A. M. Dashkevich, Z. Nurmatov, G. Melik-Andreasyan, M. Ruziev, A. Totolian","doi":"10.15789/1563-0625-pit-2867","DOIUrl":"https://doi.org/10.15789/1563-0625-pit-2867","url":null,"abstract":"The ongoing coronavirus disease (COVID-19) pandemic over the past three years has caused close attention to the problem of herd immunity, which is understood as: \"resistance to the spread of a contagious disease within a population or herd\". Collective immunity is formed both as a result of infection (natural spread of the pathogen in a population of susceptible individuals) and as a result of the use of specific vaccines. During the COVID-19 pandemic, both mechanisms for the formation of collective immunity were realized. In the first wave, there was a natural formation of collective immunity to the virus following recoveries from COVID-19 caused by pandemic spread of SARS-CoV-2. Starting from December 2020, the widespread use of specific vaccines against SARS-CoV-2 began in the USA, Great Britain, China, Russia, and a number of other countries. This launched the process of post-vaccination collective immunity formation; its features have depended on the vaccine types implemented. Currently, in those countries where vaccination and revaccination of recovered patients is widely carried out, immunity is \"hybrid\" in nature. Several commonalities should be noted in the pandemic experience: a somewhat regular, periodic (wavelike) nature of the COVID-19 epidemic process; changes in pathogen genetics in variants in all countries; and expansive mass vaccination programs in many populations. From these, we can draw some conclusions about the general trend for all countries in the formation of collective immunity during the pandemic: At the beginning of the pandemic in 2020, overall population seroprevalence did not exceed 20%. Other findings were: the highest seroprevalence rates were noted in the children's age group; pronounced regional differences were revealed; and the highest indicators were noted among medical workers. Collective immunity developed as a result of infection or illness, and in the majority of seropositive volunteers, it was represented by antibodies to both antigens. At the height of the pandemic in the summer of 2021, population seroprevalence reached 50%. This was due to both a significant number of convalescents and the start of mass vaccination campaigns. In all countries, specific differences in seroprevalence (by age, region, profession) leveled out, leading to more uniformity. During this period, the formation of \"hybrid\" immunity is clearly prominent, and the proportion of individuals with antibodies to RBD alone increased (due to vaccination with vector vaccines). Later, mass vaccination, as well as involvement of most of the population in the epidemic process due to the emergence of the highly contagious Omicron strain, raised the level of collective immunity to 80-90%. This led to a sharp decrease in COVID-19 incidence in the second half of 2022 in all countries participating in the study. In the later stages of the pandemic (2022-2023), almost 90% of seropositive volunteers had hybrid immunity, reflected as antibodies to","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":"78032870","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-doc-2741
D. Storozhilova, O. V. Kolenko, L. Danilova, L. P. Emanova, I. Vasilieva
An increase in the incidence of optic neuritis among the working-age population, as well as an unpromising prognosis for vision due to the development of optic nerve atrophy, determines the high social significance of this problem. The aim of the work is to analyze the effect of Imunofan at the parameters of cellular immunity and clinical symptoms of the disease in the complex treatment of optic neuritis associated with herpes virus infection. The study involved 37 people (37 eyes) with acute optic neuritis associated with herpes infection. The treatment regimen included the appointment of a dexamethasone solution according to a decreasing scheme, a 1% solution of the drug Emoxipin 0.5 mL and a 12.5% solution of the drug Dicynone 0.5 mL through an irrigation system implanted in the retrobulbar space, in combination with the neuroprotection drugs (Pikamilon and Semax) for 10 days. All patients were divided into 2 groups. The main group consisted of 20 patients who received Imunofan to the treatment regimen in addition. The comparison group included 17 patients who were treated only according to the method described above. The course of treatment lasted 10 days. The analysis of the data showed a more significant positive dynamics of cellular immunity parameters in those who received immunotherapy. Our studies showed the effectiveness of this drug in the complex treatment of optic neuritis associated with herpes infection, what is confirmed by the acceleration of inflammation relief, a more significant increase in visual functions of patients treated with Imunofan, and a lower percentage of optic nerve atrophy. In this group of patients, changes in the parameters of the cellular link of immunity occurred earlier and remained stable throughout the entire period of observation. According to our data, an intergroup assessment of the immunoregulatory index showed its faster increase in patients of the comparison group who received Imunofan, and reached normal values already 6 months after treatment. The clinical effectiveness of Imunofan in the complex therapy of optic neuritis associated with herpes infection was characterized by a reduction in the period of relief of signs of inflammation in the optic nerve by 2 times or more, by an increase in the maximum corrected visual acuity by 4.5 times, and by a decrease in the incidence of recurrence of optic neuritis by 2 times over a 12 months observation period.
{"title":"Dynamics of cellular immunity indicators in the complex treatment of acute optic neuritis","authors":"D. Storozhilova, O. V. Kolenko, L. Danilova, L. P. Emanova, I. Vasilieva","doi":"10.15789/1563-0625-doc-2741","DOIUrl":"https://doi.org/10.15789/1563-0625-doc-2741","url":null,"abstract":"An increase in the incidence of optic neuritis among the working-age population, as well as an unpromising prognosis for vision due to the development of optic nerve atrophy, determines the high social significance of this problem. The aim of the work is to analyze the effect of Imunofan at the parameters of cellular immunity and clinical symptoms of the disease in the complex treatment of optic neuritis associated with herpes virus infection. The study involved 37 people (37 eyes) with acute optic neuritis associated with herpes infection. The treatment regimen included the appointment of a dexamethasone solution according to a decreasing scheme, a 1% solution of the drug Emoxipin 0.5 mL and a 12.5% solution of the drug Dicynone 0.5 mL through an irrigation system implanted in the retrobulbar space, in combination with the neuroprotection drugs (Pikamilon and Semax) for 10 days. All patients were divided into 2 groups. The main group consisted of 20 patients who received Imunofan to the treatment regimen in addition. The comparison group included 17 patients who were treated only according to the method described above. The course of treatment lasted 10 days. The analysis of the data showed a more significant positive dynamics of cellular immunity parameters in those who received immunotherapy. Our studies showed the effectiveness of this drug in the complex treatment of optic neuritis associated with herpes infection, what is confirmed by the acceleration of inflammation relief, a more significant increase in visual functions of patients treated with Imunofan, and a lower percentage of optic nerve atrophy. In this group of patients, changes in the parameters of the cellular link of immunity occurred earlier and remained stable throughout the entire period of observation. According to our data, an intergroup assessment of the immunoregulatory index showed its faster increase in patients of the comparison group who received Imunofan, and reached normal values already 6 months after treatment. The clinical effectiveness of Imunofan in the complex therapy of optic neuritis associated with herpes infection was characterized by a reduction in the period of relief of signs of inflammation in the optic nerve by 2 times or more, by an increase in the maximum corrected visual acuity by 4.5 times, and by a decrease in the incidence of recurrence of optic neuritis by 2 times over a 12 months observation period.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"384 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76649970","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-cit-2797
E. Gubernatorova, A. I. Polinova, T. Yurakova, S. Nedospasov, М. S. Drutskaya
Interleukin-6 (IL-6) is a broad-spectrum cytokine involved in the immune, nervous, and endocrine regulation of many biological processes. IL-6 performs both homeostatic and pathogenic functions. It is one of the key factors in the cytokine storm in COVID-19, and it also controls the production of acute phase proteins during inflammation. IL-6 is involved in the maintenance of intestinal homeostasis and is required for both the induction of inflammation and the repair of the injured intestinal tissue. In turn, the commensal microbiota, represented by eukaryotes, prokaryotes, and viruses, is one of the key factors modulating the immune response in the gut. The predominance of certain groups of commensal microorganisms is associated with the development of intestinal inflammation, while probiotics and antibiotics are successfully used to control inflammatory bowel disease. IL-6 is also necessary to maintain the barrier function of the intestine by modulating the proliferation of intestinal cells, which is necessary for their timely renewal both in homeostasis and inflammation. It has been established that the genetic inactivation of IL6 contributes to the development of intestinal inflammation, while the involvement of IL-6 in the control of the gut microbiota composition remains unclear. To investigate this issue, we analyzed stool samples from wild-type naive mice and mice deficient in IL6 (IL-6 KO) generated on the C57Bl/6 genetic background. It has been determined that IL-6 KO shows significant changes in some taxonomic groups of commensals, which may explain the sensitivity of IL-6 KO to the development of colitis. Interestingly, the relative contents of Firmicutes and Clostridiales are significantly reduced, whereas Bacteroides are increased in IL-6 KO as compared with wild-type mice. Our data on the reduction of Firmicutes, Lactobacillaceae, and other large taxa in IL-6 deficient mice suggest that the microbiota composition of IL-6 KO mice is somewhat similar to that of mice with chronic intestinal inflammation. Our study serves as a perspective for further research on the contribution of IL-6-mediated changes in the microbiota composition to the maintenance of intestinal homeostasis and the development of chronic gut inflammation.
{"title":"Changes in the composition of the intestinal microbiota, associated with IL-6 deficiency","authors":"E. Gubernatorova, A. I. Polinova, T. Yurakova, S. Nedospasov, М. S. Drutskaya","doi":"10.15789/1563-0625-cit-2797","DOIUrl":"https://doi.org/10.15789/1563-0625-cit-2797","url":null,"abstract":"Interleukin-6 (IL-6) is a broad-spectrum cytokine involved in the immune, nervous, and endocrine regulation of many biological processes. IL-6 performs both homeostatic and pathogenic functions. It is one of the key factors in the cytokine storm in COVID-19, and it also controls the production of acute phase proteins during inflammation. IL-6 is involved in the maintenance of intestinal homeostasis and is required for both the induction of inflammation and the repair of the injured intestinal tissue. In turn, the commensal microbiota, represented by eukaryotes, prokaryotes, and viruses, is one of the key factors modulating the immune response in the gut. The predominance of certain groups of commensal microorganisms is associated with the development of intestinal inflammation, while probiotics and antibiotics are successfully used to control inflammatory bowel disease. IL-6 is also necessary to maintain the barrier function of the intestine by modulating the proliferation of intestinal cells, which is necessary for their timely renewal both in homeostasis and inflammation. It has been established that the genetic inactivation of IL6 contributes to the development of intestinal inflammation, while the involvement of IL-6 in the control of the gut microbiota composition remains unclear. To investigate this issue, we analyzed stool samples from wild-type naive mice and mice deficient in IL6 (IL-6 KO) generated on the C57Bl/6 genetic background. It has been determined that IL-6 KO shows significant changes in some taxonomic groups of commensals, which may explain the sensitivity of IL-6 KO to the development of colitis. Interestingly, the relative contents of Firmicutes and Clostridiales are significantly reduced, whereas Bacteroides are increased in IL-6 KO as compared with wild-type mice. Our data on the reduction of Firmicutes, Lactobacillaceae, and other large taxa in IL-6 deficient mice suggest that the microbiota composition of IL-6 KO mice is somewhat similar to that of mice with chronic intestinal inflammation. Our study serves as a perspective for further research on the contribution of IL-6-mediated changes in the microbiota composition to the maintenance of intestinal homeostasis and the development of chronic gut inflammation.","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":"87917445","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-cao-2758
A. V. Kolerova, O. A. Angelskaya, O. Chumasova, A. Sizikov, I. Shirinsky, V. Shirinsky, E. Blinova
Arthropathy is one of the most prevalent diseases, which are based on the destruction and remodeling of cartilage and bone tissue. The inflammation that precedes destruction can be caused by mechanical stress on the joints, or by autoimmune reactions. Recently, IL-7 is considered as one of the key cytokines that promote the production of matrix metalloproteinases, catabolic enzymes, T cell-mediated activation of monocytes, and maturation of osteoclasts. The soluble form of the IL-7 receptor can help prolong the lifespan of IL-7 and thereby it ensures the bioavailability of the cytokine and mediates effect of IL-7 on cells. The aim of this study was to determine the soluble form of the IL-7 receptor (sIL-7R) in the blood plasma of patients with rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA) and psoriasis vulgaris (PS), as well as healthy individuals. The RA patients included in the study had moderate to high disease activity according to the DAS28 index. Patients with PsA predominantly had moderate and low disease activity (DAS28) and were characterized by mild to moderate disease severity (PASI). In accordance with the PASI index, patients with PS with mild and severe severity of the disease were included in the study. All patients with OA had a metabolic phenotype that is accompanied by an elevated body mass index.sIL-7R was determined in blood plasma by enzyme-linked immunosorbent assay. It was found that in patients with arthropathy, the level of soluble form of IL-7 was increased relative to healthy individuals, with the exception of the group of patients with PsA. Also, a high concentration of sIL-7R was observed in patients with PS. Analyzing the clinical characteristics of the patients, we found that sIL-7R levels were elevated in RA and PsA patients with high disease activity by DAS28. In addition, positive correlations were found between the concentration of sIL-7R and DAS28 in RA and PsA. In patients with PsA with moderate severity of the disease (PASI), the concentration of sIL-7R was also increased relative to donor's values. On the contrary, in patients with PS, a high level of sIL-7R was noted regardless of the severity of the disease. In patients with OA, no relationship was found between sIL-7R levels and clinical parameters.Thus, an elevated level of sIL-7R in patients with arthropathy may indicate the involvement of IL-7 and its receptor system in the pathogenesis of joint diseases. The IL-7 receptor may become a promising target both in the treatment of joint diseases and other autoimmune diseases, including psoriasis.
{"title":"Comparative analysis of the expression of the soluble IL-7 receptor in patients with arthropathy","authors":"A. V. Kolerova, O. A. Angelskaya, O. Chumasova, A. Sizikov, I. Shirinsky, V. Shirinsky, E. Blinova","doi":"10.15789/1563-0625-cao-2758","DOIUrl":"https://doi.org/10.15789/1563-0625-cao-2758","url":null,"abstract":"Arthropathy is one of the most prevalent diseases, which are based on the destruction and remodeling of cartilage and bone tissue. The inflammation that precedes destruction can be caused by mechanical stress on the joints, or by autoimmune reactions. Recently, IL-7 is considered as one of the key cytokines that promote the production of matrix metalloproteinases, catabolic enzymes, T cell-mediated activation of monocytes, and maturation of osteoclasts. The soluble form of the IL-7 receptor can help prolong the lifespan of IL-7 and thereby it ensures the bioavailability of the cytokine and mediates effect of IL-7 on cells. The aim of this study was to determine the soluble form of the IL-7 receptor (sIL-7R) in the blood plasma of patients with rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis (PsA) and psoriasis vulgaris (PS), as well as healthy individuals. The RA patients included in the study had moderate to high disease activity according to the DAS28 index. Patients with PsA predominantly had moderate and low disease activity (DAS28) and were characterized by mild to moderate disease severity (PASI). In accordance with the PASI index, patients with PS with mild and severe severity of the disease were included in the study. All patients with OA had a metabolic phenotype that is accompanied by an elevated body mass index.sIL-7R was determined in blood plasma by enzyme-linked immunosorbent assay. It was found that in patients with arthropathy, the level of soluble form of IL-7 was increased relative to healthy individuals, with the exception of the group of patients with PsA. Also, a high concentration of sIL-7R was observed in patients with PS. Analyzing the clinical characteristics of the patients, we found that sIL-7R levels were elevated in RA and PsA patients with high disease activity by DAS28. In addition, positive correlations were found between the concentration of sIL-7R and DAS28 in RA and PsA. In patients with PsA with moderate severity of the disease (PASI), the concentration of sIL-7R was also increased relative to donor's values. On the contrary, in patients with PS, a high level of sIL-7R was noted regardless of the severity of the disease. In patients with OA, no relationship was found between sIL-7R levels and clinical parameters.Thus, an elevated level of sIL-7R in patients with arthropathy may indicate the involvement of IL-7 and its receptor system in the pathogenesis of joint diseases. The IL-7 receptor may become a promising target both in the treatment of joint diseases and other autoimmune diseases, including psoriasis.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86934316","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-coi-2800
O. Kurmyshkina, P. Kovchur, T. Volkova
Molecular classification, immuneheterogeneity, and the existence of distinct immunophenotypes of virus-associated cervical cancer (CeCa) remain as-yet weakly explored issues, and this is particularly true of its earliest clinical stages and pre-invasive forms: cervical intraepithelial neoplastic (CIN) lesions. The goal of the study was to identify transcriptomic landscapes of invasive CeCa at its initial progression that differ substantially in their immune-related characteristics, patterns of signaling pathways and composition of the microenvironment. Transcriptome profiling was carried out using RNA-sequencing on Illumina platform. A panel of surgical-derived tissue samples comprised human papillomavirus-positive CIN grade 1-3, cancer of FIGO IA1-IIB stages, and morphologically normal epithelium. Transcriptomic profiles were analyzed with the use of bioinformatics tools, such as gene set enrichment (GAGE) for signaling pathways, xCell enrichment for cell composition identification, and PREDA positional analysis of genomic data. Hierarchical clustering revealed heterogeneity of transcriptomic profiles within the early-stage CeCa, namely, the existence of two clusters of tumor samples and three functional patterns of genes showing coordinately altered expression. Pathway enrichment analysis on genes differently expressed between the two clusters/groups of CeCa samples (‘A' and ‘B') and CIN (group ‘C') suggested that invasive tumor progression in groups ‘A' and ‘B' might rely on immunologically dissimilar mechanisms. xCell analysis confirmed heterogeneity of changes in the abundancies of cell populations when comparing CeCa sample groups and CIN, along with differences in immune and stromal scores. PREDA demonstrated that these transcriptomic differences could be linked to different chromosomal regions and co-localized with particular gene families and potentially the reported virus integration hotspots. Overall, the existence and detectability of different transcriptomic immune-based phenotypes of invasive CeCa at its initial stages of progression is shown, which may provide new options to broaden the knowledge and applicability of target and immune anti-cancer therapy.
{"title":"Characteristics of immune-active and immune-silent phenotypes of early-stage cervical carcinoma as revealed by transcriptome sequencing","authors":"O. Kurmyshkina, P. Kovchur, T. Volkova","doi":"10.15789/1563-0625-coi-2800","DOIUrl":"https://doi.org/10.15789/1563-0625-coi-2800","url":null,"abstract":"Molecular classification, immuneheterogeneity, and the existence of distinct immunophenotypes of virus-associated cervical cancer (CeCa) remain as-yet weakly explored issues, and this is particularly true of its earliest clinical stages and pre-invasive forms: cervical intraepithelial neoplastic (CIN) lesions. The goal of the study was to identify transcriptomic landscapes of invasive CeCa at its initial progression that differ substantially in their immune-related characteristics, patterns of signaling pathways and composition of the microenvironment. Transcriptome profiling was carried out using RNA-sequencing on Illumina platform. A panel of surgical-derived tissue samples comprised human papillomavirus-positive CIN grade 1-3, cancer of FIGO IA1-IIB stages, and morphologically normal epithelium. Transcriptomic profiles were analyzed with the use of bioinformatics tools, such as gene set enrichment (GAGE) for signaling pathways, xCell enrichment for cell composition identification, and PREDA positional analysis of genomic data. Hierarchical clustering revealed heterogeneity of transcriptomic profiles within the early-stage CeCa, namely, the existence of two clusters of tumor samples and three functional patterns of genes showing coordinately altered expression. Pathway enrichment analysis on genes differently expressed between the two clusters/groups of CeCa samples (‘A' and ‘B') and CIN (group ‘C') suggested that invasive tumor progression in groups ‘A' and ‘B' might rely on immunologically dissimilar mechanisms. xCell analysis confirmed heterogeneity of changes in the abundancies of cell populations when comparing CeCa sample groups and CIN, along with differences in immune and stromal scores. PREDA demonstrated that these transcriptomic differences could be linked to different chromosomal regions and co-localized with particular gene families and potentially the reported virus integration hotspots. Overall, the existence and detectability of different transcriptomic immune-based phenotypes of invasive CeCa at its initial stages of progression is shown, which may provide new options to broaden the knowledge and applicability of target and immune anti-cancer therapy.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87999461","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-2770
E. Kuklina, N. Glebezdina
Helper T cells producing IL-17 (Th17) have high plasticity: restimulation of lymphocytes in an inflammatory environment can induce their transformation into cells with another phenotype, and a shift towards Th1 is the most common. The result of this transformation is the appearance of cells expressing along with the classical markers of Th17 cells key Th1-associated molecules. In its most general form, this population is represented by CD4+CD161+CCR6+CXCR3+IL-17+IFNγ+Т cells, and in the current literature it is most often referred to as Th17.1. Some Th17.1 cells can completely lose the production of IL-17, while maintaining the expression of other Th17-associated molecules; these are the so-called ex-Th17 cells (CD4+CD161+CCR6+CXCR3+IL-17- IFNγ+Т cells). Consequently, the population of Th1-polarized Th17 includes Th17.1, ex-Th17 cells and a number of additional transitional forms. It has unique functional properties – an increased pro-inflammatory potential and the ability to overcome histohematic barriers. It is these cells that are currently assigned a key role in the pathogenesis of many autoimmune diseases, and the process of Th17 redifferentiation into Th1 is considered as a promising therapeutic target. However, the development of this direction is complicated by the weak comparability of data on the size of such a population. The analysis of methods for determining Th1-polarized Th17 in vivo and in vitro, carried out in this work, made it possible to resolve these contradictions and develop optimal approaches to identifying this population. In most studies, especially clinical ones, it is identified by co-expression of key cytokines (IL-17/IFNγ) or chemokine receptors (CCR6/CXCR3), rarely by their combination. In this approach, co-expression of CCR6/ CXCR3 marks the total population of Th1-like Th17, including both Th17.1 and ex-Th17, while co-expression of IL-17/IFNγ cytokines identifies only Th17.1 cells, and the subpopulation of ex-Th17 is misclassified as classic Th1 in this case. Such “underestimation” of the ex-Th17 subpopulation significantly marks down the results, since it is ex-Th17 that accounts for the bulk of Th1-like Th17. And only a simultaneous assessment of the co-expression of cytokines and Th17-associated membrane molecules allows identification Th17.1 and exTh17 cells separately, which is important to consider when interpreting data on the problem and when planning clinical trials.
{"title":"Identification of Th1-polarized Th17 cells: solving the problem","authors":"E. Kuklina, N. Glebezdina","doi":"10.15789/1563-0625-iot-2770","DOIUrl":"https://doi.org/10.15789/1563-0625-iot-2770","url":null,"abstract":"Helper T cells producing IL-17 (Th17) have high plasticity: restimulation of lymphocytes in an inflammatory environment can induce their transformation into cells with another phenotype, and a shift towards Th1 is the most common. The result of this transformation is the appearance of cells expressing along with the classical markers of Th17 cells key Th1-associated molecules. In its most general form, this population is represented by CD4+CD161+CCR6+CXCR3+IL-17+IFNγ+Т cells, and in the current literature it is most often referred to as Th17.1. Some Th17.1 cells can completely lose the production of IL-17, while maintaining the expression of other Th17-associated molecules; these are the so-called ex-Th17 cells (CD4+CD161+CCR6+CXCR3+IL-17- IFNγ+Т cells). Consequently, the population of Th1-polarized Th17 includes Th17.1, ex-Th17 cells and a number of additional transitional forms. It has unique functional properties – an increased pro-inflammatory potential and the ability to overcome histohematic barriers. It is these cells that are currently assigned a key role in the pathogenesis of many autoimmune diseases, and the process of Th17 redifferentiation into Th1 is considered as a promising therapeutic target. However, the development of this direction is complicated by the weak comparability of data on the size of such a population. The analysis of methods for determining Th1-polarized Th17 in vivo and in vitro, carried out in this work, made it possible to resolve these contradictions and develop optimal approaches to identifying this population. In most studies, especially clinical ones, it is identified by co-expression of key cytokines (IL-17/IFNγ) or chemokine receptors (CCR6/CXCR3), rarely by their combination. In this approach, co-expression of CCR6/ CXCR3 marks the total population of Th1-like Th17, including both Th17.1 and ex-Th17, while co-expression of IL-17/IFNγ cytokines identifies only Th17.1 cells, and the subpopulation of ex-Th17 is misclassified as classic Th1 in this case. Such “underestimation” of the ex-Th17 subpopulation significantly marks down the results, since it is ex-Th17 that accounts for the bulk of Th1-like Th17. And only a simultaneous assessment of the co-expression of cytokines and Th17-associated membrane molecules allows identification Th17.1 and exTh17 cells separately, which is important to consider when interpreting data on the problem and when planning clinical trials.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"75 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86770715","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-sco-2830
M. Shevchenko, D. E. Murova, E. Servuli
Daily inhaled antigens induce cellular immune response in the airways. In case of allergens, allergic airway inflammation is usually represented by eosinophils, however, neutrophil infiltration is also observed during severe asthma. Animal models contribute to investigation of the mechanisms that involve the switching to eosinophil- or neutrophil-mediated inflammation. Data about the spatial location of eosinophils and neutrophils in the airways are necessary for both the understanding of allergic airway inflammation mechanisms and the drag potential estimation, however, not completely investigated. In the present study, we characterized the model of Aspergillus fumigatus extract-induced allergic airway inflammation that allowed investigating the early stage of inflammation development. The model adequacy was confirmed according to the blood and bronchoalveolar lavage eosinophilia. Using immunohistochemical staining of conducting airway as a whole-mount and confocal laser scanning microscopy, we estimated neutrophil and eosinophil spatial location: in the luminal side of the epithelium, in the airway wall or in the submucosal compartment close to the smooth muscle layer. An allergic airway response activation was detected upon significant elevation of blood eosinophil percentage compared to intact mice. Simultaneously, the number of eosinophils in the bronchoalveolar lavage was also significantly increased compared to the intact mice. At this time point, eosinophils predominated both in bronchoalveolar lavages and in conducting airway mucosa compared to neutrophils. Spatial location of conducting airway mucosal cell analysis demonstrated that eosinophils mostly located in the submucosal compartment, in a lesser extent in the airway wall, and a few eosinophils were detected in the luminal side of the epithelium. Neutrophils mainly infiltrated the luminal side of the epithelium, and a few neutrophils were detected in the submucosal compartment, while no neutrophils were detected in the airway wall. The data suggests that in response to the further allergen challenge, evidently eosinophils but not neutrophils will migrate through the airway wall to the airway lumen. Thus, eosinophils can be expected to damage airway epithelium in allergic airway inflammation development. Simultaneously, neutrophils located in close proximity to the smooth muscle layer together with eosinophils can contribute to bronchoconstriction induction.
{"title":"Spatial characteristics of neutrophils and eosinophils in conducting airway mucosa of mice with induced allergic airway inflammation","authors":"M. Shevchenko, D. E. Murova, E. Servuli","doi":"10.15789/1563-0625-sco-2830","DOIUrl":"https://doi.org/10.15789/1563-0625-sco-2830","url":null,"abstract":"Daily inhaled antigens induce cellular immune response in the airways. In case of allergens, allergic airway inflammation is usually represented by eosinophils, however, neutrophil infiltration is also observed during severe asthma. Animal models contribute to investigation of the mechanisms that involve the switching to eosinophil- or neutrophil-mediated inflammation. Data about the spatial location of eosinophils and neutrophils in the airways are necessary for both the understanding of allergic airway inflammation mechanisms and the drag potential estimation, however, not completely investigated. In the present study, we characterized the model of Aspergillus fumigatus extract-induced allergic airway inflammation that allowed investigating the early stage of inflammation development. The model adequacy was confirmed according to the blood and bronchoalveolar lavage eosinophilia. Using immunohistochemical staining of conducting airway as a whole-mount and confocal laser scanning microscopy, we estimated neutrophil and eosinophil spatial location: in the luminal side of the epithelium, in the airway wall or in the submucosal compartment close to the smooth muscle layer. An allergic airway response activation was detected upon significant elevation of blood eosinophil percentage compared to intact mice. Simultaneously, the number of eosinophils in the bronchoalveolar lavage was also significantly increased compared to the intact mice. At this time point, eosinophils predominated both in bronchoalveolar lavages and in conducting airway mucosa compared to neutrophils. Spatial location of conducting airway mucosal cell analysis demonstrated that eosinophils mostly located in the submucosal compartment, in a lesser extent in the airway wall, and a few eosinophils were detected in the luminal side of the epithelium. Neutrophils mainly infiltrated the luminal side of the epithelium, and a few neutrophils were detected in the submucosal compartment, while no neutrophils were detected in the airway wall. The data suggests that in response to the further allergen challenge, evidently eosinophils but not neutrophils will migrate through the airway wall to the airway lumen. Thus, eosinophils can be expected to damage airway epithelium in allergic airway inflammation development. Simultaneously, neutrophils located in close proximity to the smooth muscle layer together with eosinophils can contribute to bronchoconstriction induction.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90280432","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-mhs-2680
A. Yu. Stolbovaya, I. V. Smirnov
MICA and MICB are non-classical MHC molecules that indicate cellular stress. They act as ligands for NKG2D receptors found on NK cells, thereby triggering a cytotoxic response against damaged, infected, or transformed cells. The production of soluble forms of MICA/MICB occurs via the cleavage of their extracellular domains (ECDs). The expression of MICA/MICB molecules in tumor sections or the levels of their soluble forms in blood have potential as diagnostic tools for cancer. They can predict important clinical outcomes for cancer patients, such as overall and recurrence-free survival. However, their extensive molecular polymorphism complicates the development of monoclonal antibodies (mAbs) for diagnostic use. Therefore, the diagnostic value of mAb-based assays may vary depending on the frequencies of allelic variants in local human populations. We examined the ECD amino acid sequences of more than 280 MICA and 50 MICB allelic variants. Additionally, we identified 172 and 58 single nucleotide polymorphisms (SNPs) located in the coding regions of the respective genes and resulting in amino acid replacements. The most frequent amino acid replacements (> 10%) in the ECD occur at 11 and 4 sites of MICA and MICB, respectively. We found that the frequencies of SNPs in the identified hot spots strongly correlate with each other in different human populations, despite the diversity of allelic variant frequencies. The functional role of only one site is known. The replacement of valine with methionine at position 152 enhances the affinity of MICA to NKG2D receptor. As the hot spots are dispersed throughout the entire ECD sequences, they may play a role other than modulating affinity with the NKG2D receptor interaction. We recommend that Ag sets used to validate anti-MICA/MICB mAbs meet two criteria. First, they should include both MICA and MICB alleles, as these genes have highly similar sequences. Second, the alleles should cover the variability observed in the identified hot spots.
{"title":"Mutation hot spots in MICA/MICB extracellular domains","authors":"A. Yu. Stolbovaya, I. V. Smirnov","doi":"10.15789/1563-0625-mhs-2680","DOIUrl":"https://doi.org/10.15789/1563-0625-mhs-2680","url":null,"abstract":"MICA and MICB are non-classical MHC molecules that indicate cellular stress. They act as ligands for NKG2D receptors found on NK cells, thereby triggering a cytotoxic response against damaged, infected, or transformed cells. The production of soluble forms of MICA/MICB occurs via the cleavage of their extracellular domains (ECDs). The expression of MICA/MICB molecules in tumor sections or the levels of their soluble forms in blood have potential as diagnostic tools for cancer. They can predict important clinical outcomes for cancer patients, such as overall and recurrence-free survival. However, their extensive molecular polymorphism complicates the development of monoclonal antibodies (mAbs) for diagnostic use. Therefore, the diagnostic value of mAb-based assays may vary depending on the frequencies of allelic variants in local human populations. We examined the ECD amino acid sequences of more than 280 MICA and 50 MICB allelic variants. Additionally, we identified 172 and 58 single nucleotide polymorphisms (SNPs) located in the coding regions of the respective genes and resulting in amino acid replacements. The most frequent amino acid replacements (> 10%) in the ECD occur at 11 and 4 sites of MICA and MICB, respectively. We found that the frequencies of SNPs in the identified hot spots strongly correlate with each other in different human populations, despite the diversity of allelic variant frequencies. The functional role of only one site is known. The replacement of valine with methionine at position 152 enhances the affinity of MICA to NKG2D receptor. As the hot spots are dispersed throughout the entire ECD sequences, they may play a role other than modulating affinity with the NKG2D receptor interaction. We recommend that Ag sets used to validate anti-MICA/MICB mAbs meet two criteria. First, they should include both MICA and MICB alleles, as these genes have highly similar sequences. Second, the alleles should cover the variability observed in the identified hot spots.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"10 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134903257","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-imo-2725
O. Moskalets
Periprosthetic joint infection still remains a clinical challenge since accurate definition of this condition and reliable laboratory markers have not been established yet. This study aimed to evaluate the benefit of some lymphocyte and monocyte subset determination in patients with periprosthetic joint infection and non-infectious arthroplasty failure. Thirty-four patients with chronic periprosthetic joint infection, 12 patients with non-infectious arthroplasty and 30 healthy persons were included in the study. The counts of CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+, CD3+HLA-DR+, CD4+CD45RACD45RО+, CD4+CD45RA+ CD45RО- and CD14+ HLA-DR+ subsets in peripheral blood were assessed by flow cytometry. The assessment of the intensity of antigen expression was carried out according to mean fluorescence intensity. A significant increase in CD3+CD4+ subsets (p < 0,01) and a significant decrease in CD3-CD16+CD56+ subsets (p < 0,005) were revealed in patients with periprosthetic joint infection compared to the healthy controls. The content of CD19+ lymphocytes in these patients was significantly higher than in aseptic ones (p < 0,005); the latter group was also characterized by more pronounced increase in the number of activated T lymphocytes (CD3+HLA-DR+) compared to controls (p < 0,001). Patients with periprosthetic joint infection showed decreased “naïve” T lymphocytes (CD4+CD45RA+CD45RO-) count compared to aseptic ones (p < 0,05), and both groups showed a decrease counts compared to controls (p < 0,001). On the contrary, memory T lymphocyte (CD4+CD45RACD45RO+) count was significantly increased in both compared groups (p < 0,05). Patients with periprosthetic joint infection compared with other two groups demonstrated a significant decrease in the number of activated monocytes (CD14+HLA-DR+) and pronounced decrease in the expression intensity of this marker on cell membrane (p < 0,05 and p < 0,001, respectively). Thus, evaluation of lymphocyte and monocyte subsets, including expression of cell activation antigens could be useful as additional laboratory test in combination with other conventional methods for differentiation between periprosthetic joint infection and aseptic arthroplasty failure.
{"title":"Immunological markers of arthroplasty failure","authors":"O. Moskalets","doi":"10.15789/1563-0625-imo-2725","DOIUrl":"https://doi.org/10.15789/1563-0625-imo-2725","url":null,"abstract":"Periprosthetic joint infection still remains a clinical challenge since accurate definition of this condition and reliable laboratory markers have not been established yet. This study aimed to evaluate the benefit of some lymphocyte and monocyte subset determination in patients with periprosthetic joint infection and non-infectious arthroplasty failure. Thirty-four patients with chronic periprosthetic joint infection, 12 patients with non-infectious arthroplasty and 30 healthy persons were included in the study. The counts of CD3+, CD3+CD4+, CD3+CD8+, CD19+, CD3-CD16+CD56+, CD3+HLA-DR+, CD4+CD45RACD45RО+, CD4+CD45RA+ CD45RО- and CD14+ HLA-DR+ subsets in peripheral blood were assessed by flow cytometry. The assessment of the intensity of antigen expression was carried out according to mean fluorescence intensity. A significant increase in CD3+CD4+ subsets (p < 0,01) and a significant decrease in CD3-CD16+CD56+ subsets (p < 0,005) were revealed in patients with periprosthetic joint infection compared to the healthy controls. The content of CD19+ lymphocytes in these patients was significantly higher than in aseptic ones (p < 0,005); the latter group was also characterized by more pronounced increase in the number of activated T lymphocytes (CD3+HLA-DR+) compared to controls (p < 0,001). Patients with periprosthetic joint infection showed decreased “naïve” T lymphocytes (CD4+CD45RA+CD45RO-) count compared to aseptic ones (p < 0,05), and both groups showed a decrease counts compared to controls (p < 0,001). On the contrary, memory T lymphocyte (CD4+CD45RACD45RO+) count was significantly increased in both compared groups (p < 0,05). Patients with periprosthetic joint infection compared with other two groups demonstrated a significant decrease in the number of activated monocytes (CD14+HLA-DR+) and pronounced decrease in the expression intensity of this marker on cell membrane (p < 0,05 and p < 0,001, respectively). Thus, evaluation of lymphocyte and monocyte subsets, including expression of cell activation antigens could be useful as additional laboratory test in combination with other conventional methods for differentiation between periprosthetic joint infection and aseptic arthroplasty failure.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"91 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76625602","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-pie-2755
V. Gorodin, V. A. Matushkina, V. N. Chapurina, A. I. Menyailo, S. Kovaleva, E. I. Dydyshko
The key role of neutrophilic granulocytes (NG) in the pathogenesis of COVID-19 makes them new targets for therapeutic approaches and of influencing the course and outcome of the disease, restoring changes in the phenotype and functions of NG. Synthetic peptides or polypeptide complexes of action are the most promising in the treatment of COVID-19. Aim: to reveal the effects of the influence of the hexapeptide (HP) – Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on the phenotype of functionally significant NG subsets in moderate COVID-19.The study examined patients 61 (57-71) years old (n = 45) in the acute period of COVID-19 – study group1 (SG1). In vitro, samples SG1 were incubated with HP (106 g/L, 60 min, 37 °C) – study group2 (SG2). The number of NG subsets was evaluated: CD16+IFNα/βR1+CD119+, CD16+IFNα/βR1+CD119- , CD16+IFNα/βR1+CD119+, CD64- CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and phenotype by membrane receptor expression density (MFI) (FC 500, Beckman Coulter, USA); NG phagocytic activity was tested before and after incubation with HP. The comparison group (GS) – of 22 volunteers examined in the pre-COVID period.It was revealed that unidirectional effects of HP in vitro contributing to the restoration of the phenotype of subsets CD16+IFNα/βR1- CD119+, CD16+IFNα/βR1+CD119- to CG indicators. There was a decrease in MFI CD16 (p < 0.05) in both subsets; MFI CD119 (p < 0.05) in the CD16+IFNα/βR1- CD119+NG subset, MFI IFNa/βR1 in the CD16+IFNα/βR1+CD119- NG subset. The effects of HP on the phenotype of CD16+IFNα/βR1+CD119+NG subsets in 76% of cases were manifested by a decrease in MFI CD16 (p<0.05), an increase in MFI IFNα/βR1 and CD119 (p1, 2<0.05), and in 24% of cases a decrease in MFI IFNα/βR1 (p<0.05). HP in vitro remodeling of the phenotypes subsets CD64- CD16+CD32+CD11b+ and CD64+CD16+CD32+CD11b+ were established, providing the usefulness of effector functions from hyperactivated to normal. In the CD64- CD16+CD32+CD11b+ subset, there was a decrease in MFI CD16 and CD11b to the indicators CG (p1, 2 < 0.05). Recovery of the NG phenotype under the influence of HP led to the restoration of the phagocytic function of NG.Positive effects of HP in vitro on the phenotypes of subsets actively and NGfunctions in COVID-19 open up prospects for the creation of new methods of immunotherapy to restore NG dysfunctions.
{"title":"Pleiotropic immunomodulating effects of peptide Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on various subsets of neutrophilic granulocytes and their phenotype in patients with COVID-19 in vitro","authors":"V. Gorodin, V. A. Matushkina, V. N. Chapurina, A. I. Menyailo, S. Kovaleva, E. I. Dydyshko","doi":"10.15789/1563-0625-pie-2755","DOIUrl":"https://doi.org/10.15789/1563-0625-pie-2755","url":null,"abstract":"The key role of neutrophilic granulocytes (NG) in the pathogenesis of COVID-19 makes them new targets for therapeutic approaches and of influencing the course and outcome of the disease, restoring changes in the phenotype and functions of NG. Synthetic peptides or polypeptide complexes of action are the most promising in the treatment of COVID-19. Aim: to reveal the effects of the influence of the hexapeptide (HP) – Arginyl-alpha-Aspartyl-Lysyl-Valyl-Tyrosyl-Arginine on the phenotype of functionally significant NG subsets in moderate COVID-19.The study examined patients 61 (57-71) years old (n = 45) in the acute period of COVID-19 – study group1 (SG1). In vitro, samples SG1 were incubated with HP (106 g/L, 60 min, 37 °C) – study group2 (SG2). The number of NG subsets was evaluated: CD16+IFNα/βR1+CD119+, CD16+IFNα/βR1+CD119- , CD16+IFNα/βR1+CD119+, CD64- CD16+CD32+CD11b+, CD64+CD16+CD32+CD11b+ and phenotype by membrane receptor expression density (MFI) (FC 500, Beckman Coulter, USA); NG phagocytic activity was tested before and after incubation with HP. The comparison group (GS) – of 22 volunteers examined in the pre-COVID period.It was revealed that unidirectional effects of HP in vitro contributing to the restoration of the phenotype of subsets CD16+IFNα/βR1- CD119+, CD16+IFNα/βR1+CD119- to CG indicators. There was a decrease in MFI CD16 (p < 0.05) in both subsets; MFI CD119 (p < 0.05) in the CD16+IFNα/βR1- CD119+NG subset, MFI IFNa/βR1 in the CD16+IFNα/βR1+CD119- NG subset. The effects of HP on the phenotype of CD16+IFNα/βR1+CD119+NG subsets in 76% of cases were manifested by a decrease in MFI CD16 (p<0.05), an increase in MFI IFNα/βR1 and CD119 (p1, 2<0.05), and in 24% of cases a decrease in MFI IFNα/βR1 (p<0.05). HP in vitro remodeling of the phenotypes subsets CD64- CD16+CD32+CD11b+ and CD64+CD16+CD32+CD11b+ were established, providing the usefulness of effector functions from hyperactivated to normal. In the CD64- CD16+CD32+CD11b+ subset, there was a decrease in MFI CD16 and CD11b to the indicators CG (p1, 2 < 0.05). Recovery of the NG phenotype under the influence of HP led to the restoration of the phagocytic function of NG.Positive effects of HP in vitro on the phenotypes of subsets actively and NGfunctions in COVID-19 open up prospects for the creation of new methods of immunotherapy to restore NG dysfunctions.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":"103 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78469703","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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