Pub Date : 2021-06-22DOI: 10.15789/1563-0625-ipo-2170
V. Timganova, M. Bochkova, M. Rayev, P. Khramtsov, S. Zamorina
The embryo, being half an antigenically “foreign” organism, should elicit a maternal immune response. During evolution, however, the mechanisms ensuring successful development of pregnancy have been formed. In particular, among factors providing immune tolerance during pregnancy are some proteins associated with pregnancy. The pregnancy-specific β 1-glycoprotein (PSG, PSG1; SP1; PSβG1) is a dominant fetoplacental protein produced by cyto- and syncytiotrophoblast cells, and it exhibits immunosuppressive properties. Our team of authors possesses a patented method for obtaining native human PSG preparation from blood serum of pregnant women, a mixture of PSG1, PSG3, PSG7, PSG9, and their isoforms and precursors. This review presents an analysis of our results for the period from 2015 to 2020. We studied the immunoregu-latory effects of the obtained PSG preparation at concentrations comparable to those observed in pregnancy (1, 10, 100 |ag/mL). The study was performed with peripheral blood cells obtained from non-pregnant women. It was found that PSG significantly increased the percentage of adaptive Tregs in vitro, as well as expression of CTLA-4, GITR, and production of IL-10 by these cells. It has been shown that PSG has a stimulating effect upon indoleamine-2,3-dioxygenase (IDO) activity of peripheral blood monocytes. For Th17 cells, we have demonstrated that PSG can suppress differentiation and proliferation of these cells, along with reduced production of critical proinflammatory cytokines (IL-8, IL-10, IL-17, IFNγ, MCP-1, TNF α). As for the memory T cells, PSG suppressed CD25 expression and IL-2 production by them, along with simultaneous decreased expression of Gfi1, hnRNPLL genes, thus preventing the formation of the “mature” CD45R0 isoform. PSG has been shown to inhibit naive T cells’ conversion to the terminally differentiated effector subpopulation of helper T cells. When analyzing PSG effects upon cytokine profile of immunocompetent cells, it was found that the protein predominantly suppresses the Th1 cytokine production by the studied cell types, and regulates the Th2 cytokine production in divergent manner. The results obtained are consistent with general concept of immunosuppression during pregnancy. Thus, PSG could be one of the factors preventing formation and implementation of immune response to placental antigens.
{"title":"Immunoregulatory potential of pregnancy-specific β1-glycoprotein","authors":"V. Timganova, M. Bochkova, M. Rayev, P. Khramtsov, S. Zamorina","doi":"10.15789/1563-0625-ipo-2170","DOIUrl":"https://doi.org/10.15789/1563-0625-ipo-2170","url":null,"abstract":"The embryo, being half an antigenically “foreign” organism, should elicit a maternal immune response. During evolution, however, the mechanisms ensuring successful development of pregnancy have been formed. In particular, among factors providing immune tolerance during pregnancy are some proteins associated with pregnancy. The pregnancy-specific β 1-glycoprotein (PSG, PSG1; SP1; PSβG1) is a dominant fetoplacental protein produced by cyto- and syncytiotrophoblast cells, and it exhibits immunosuppressive properties. Our team of authors possesses a patented method for obtaining native human PSG preparation from blood serum of pregnant women, a mixture of PSG1, PSG3, PSG7, PSG9, and their isoforms and precursors. This review presents an analysis of our results for the period from 2015 to 2020. We studied the immunoregu-latory effects of the obtained PSG preparation at concentrations comparable to those observed in pregnancy (1, 10, 100 |ag/mL). The study was performed with peripheral blood cells obtained from non-pregnant women. It was found that PSG significantly increased the percentage of adaptive Tregs in vitro, as well as expression of CTLA-4, GITR, and production of IL-10 by these cells. It has been shown that PSG has a stimulating effect upon indoleamine-2,3-dioxygenase (IDO) activity of peripheral blood monocytes. For Th17 cells, we have demonstrated that PSG can suppress differentiation and proliferation of these cells, along with reduced production of critical proinflammatory cytokines (IL-8, IL-10, IL-17, IFNγ, MCP-1, TNF α). As for the memory T cells, PSG suppressed CD25 expression and IL-2 production by them, along with simultaneous decreased expression of Gfi1, hnRNPLL genes, thus preventing the formation of the “mature” CD45R0 isoform. PSG has been shown to inhibit naive T cells’ conversion to the terminally differentiated effector subpopulation of helper T cells. When analyzing PSG effects upon cytokine profile of immunocompetent cells, it was found that the protein predominantly suppresses the Th1 cytokine production by the studied cell types, and regulates the Th2 cytokine production in divergent manner. The results obtained are consistent with general concept of immunosuppression during pregnancy. Thus, PSG could be one of the factors preventing formation and implementation of immune response to placental antigens.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67110067","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 : 2021-06-22DOI: 10.15789/1563-0625-peo-2222
I. Shirinsky, V. Shirinsky
Here we review literature data on properties of a member of nuclear hormone receptors - peroxisome proliferator-activated receptor-α. It was shown that PPARα was expressed on different cells including dendritic cells, macrophages, B- and T-cells. We discuss structure of natural and synthetic ligands of PPARa, molecular and cellular mechanisms of PPARa regulation of lipid and carbohydrate cellular metabolism. PPARa activity in hepatocytes results in decrease of intracellular concentrations of lipid acids. This leads to reduction of VLDL cholesterol, increase in HDL-cholesterol and decrease in triglycerides in plasma of patients taking PPARα agonists. Modulation of PPARa activity may change multiple biological effects of glucocorticoids (GCS) and insulin resistance. It is assumed that PPARα agonists reduce side effects of GCS and at the same time enhance their anti-inflammatory activity due to transrepression of NF-kB. We analyzed the results of several randomized studies, meta-analyses devoted to assessment of efficacy and safety of PPARa agonist fenofibrate in patients with type 2 diabetes mellitus with high risk of micro- and macrovascular events. The studies showed good safety profile of monotherapy with fibrates as well as of their combinations with statins, ezetimibe. Fibrates reduced not only cardiovascular events but also overall mortality. We present the data on the role of PPARa in control of glucose and lipid metabolism in subpopulations of innate and adaptive immunity cells. The data show that glucose and lipid metabolism play an important role in the fate of cells of innate and adaptive immunity. The metabolic state of lymphocytes has dynamic nature and depends on their functional activity. Transition from dormant cells with relatively low metabolism rate to activated and proliferating cells is accompanied with increase of metabolic demands. This transition is supported with the switch from oxidative metabolism to anaerobic glycolysis (Warburg effect) after antigen recognition by T-cells and B-cells. It was shown that granulocytes, dendritic cells and M1 macrophages were dependent on glucose metabolism during their activation while M2 macrophages were dependent on fatty acids oxidation. In contrast with lymphocytes, activated myeloid cells do not proliferate well but still have increased glycolysis which is necessary for their effector function. It is stressed that modulation of immune cells metabolism via PPARα gives new opportunities to modulate intensity and duration of immune responses in chronic diseases. We analyze studies performed on animal models of some chronic diseases, human patients with rheumatoid arthritis and different phenotypes of osteoarthritis. Most of the studies showed clinical efficacy and pleiotropic effects of PPARα agonists: antiinflammatory, immunomodulating and lipid modulating, primarily reduction of triglycerides and increase in HDL-C. The presented literature data suggest efficacy of PPARα agonists agains
{"title":"Pleiotropic effects of PPAR-α – from benchside to bedside","authors":"I. Shirinsky, V. Shirinsky","doi":"10.15789/1563-0625-peo-2222","DOIUrl":"https://doi.org/10.15789/1563-0625-peo-2222","url":null,"abstract":"Here we review literature data on properties of a member of nuclear hormone receptors - peroxisome proliferator-activated receptor-α. It was shown that PPARα was expressed on different cells including dendritic cells, macrophages, B- and T-cells. We discuss structure of natural and synthetic ligands of PPARa, molecular and cellular mechanisms of PPARa regulation of lipid and carbohydrate cellular metabolism. PPARa activity in hepatocytes results in decrease of intracellular concentrations of lipid acids. This leads to reduction of VLDL cholesterol, increase in HDL-cholesterol and decrease in triglycerides in plasma of patients taking PPARα agonists. Modulation of PPARa activity may change multiple biological effects of glucocorticoids (GCS) and insulin resistance. It is assumed that PPARα agonists reduce side effects of GCS and at the same time enhance their anti-inflammatory activity due to transrepression of NF-kB. We analyzed the results of several randomized studies, meta-analyses devoted to assessment of efficacy and safety of PPARa agonist fenofibrate in patients with type 2 diabetes mellitus with high risk of micro- and macrovascular events. The studies showed good safety profile of monotherapy with fibrates as well as of their combinations with statins, ezetimibe. Fibrates reduced not only cardiovascular events but also overall mortality. We present the data on the role of PPARa in control of glucose and lipid metabolism in subpopulations of innate and adaptive immunity cells. The data show that glucose and lipid metabolism play an important role in the fate of cells of innate and adaptive immunity. The metabolic state of lymphocytes has dynamic nature and depends on their functional activity. Transition from dormant cells with relatively low metabolism rate to activated and proliferating cells is accompanied with increase of metabolic demands. This transition is supported with the switch from oxidative metabolism to anaerobic glycolysis (Warburg effect) after antigen recognition by T-cells and B-cells. It was shown that granulocytes, dendritic cells and M1 macrophages were dependent on glucose metabolism during their activation while M2 macrophages were dependent on fatty acids oxidation. In contrast with lymphocytes, activated myeloid cells do not proliferate well but still have increased glycolysis which is necessary for their effector function. It is stressed that modulation of immune cells metabolism via PPARα gives new opportunities to modulate intensity and duration of immune responses in chronic diseases. We analyze studies performed on animal models of some chronic diseases, human patients with rheumatoid arthritis and different phenotypes of osteoarthritis. Most of the studies showed clinical efficacy and pleiotropic effects of PPARα agonists: antiinflammatory, immunomodulating and lipid modulating, primarily reduction of triglycerides and increase in HDL-C. The presented literature data suggest efficacy of PPARα agonists agains","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67111123","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 : 2021-06-22DOI: 10.15789/1563-0625-rai-2111
S. V. Timofeeva, A. Sitkovskaya, I. Novikova, M. A. Ezhova, E. P. Lysenko, O. Kit
Glioblastoma remains the most common and aggressive primary brain tumor today. Because of the neuroanatomical location of glioblastoma, conventional chemotherapy and radiation therapy have limited efficacy in patients with these tumors. Over the past decade, antitumor immunotherapy has become widespread among modern therapeutic approaches. The importance of immunotherapeutic methods lies in their ability to increase the effectiveness of cancer treatment and prevent relapses by enhancing the systemic and local immune response against tumor cells.One of the most promising directions in modern immunotherapy is CAR-T therapy, or adoptive cell therapy using genetically modified T-lymphocytes. The functional advantage of CAR-T therapy is its ability to genetically modify lymphocytes, leading to their activation in vitro.This review examines the key principles of CAR-T therapy and analyzes the published results of clinical trials for the treatment of glioblastoma using several modifications of CAR-T cells.
{"title":"Recent achievements in CAR-T cell immunotherapy for glioblastoma treatment","authors":"S. V. Timofeeva, A. Sitkovskaya, I. Novikova, M. A. Ezhova, E. P. Lysenko, O. Kit","doi":"10.15789/1563-0625-rai-2111","DOIUrl":"https://doi.org/10.15789/1563-0625-rai-2111","url":null,"abstract":"Glioblastoma remains the most common and aggressive primary brain tumor today. Because of the neuroanatomical location of glioblastoma, conventional chemotherapy and radiation therapy have limited efficacy in patients with these tumors. Over the past decade, antitumor immunotherapy has become widespread among modern therapeutic approaches. The importance of immunotherapeutic methods lies in their ability to increase the effectiveness of cancer treatment and prevent relapses by enhancing the systemic and local immune response against tumor cells.One of the most promising directions in modern immunotherapy is CAR-T therapy, or adoptive cell therapy using genetically modified T-lymphocytes. The functional advantage of CAR-T therapy is its ability to genetically modify lymphocytes, leading to their activation in vitro.This review examines the key principles of CAR-T therapy and analyzes the published results of clinical trials for the treatment of glioblastoma using several modifications of CAR-T cells.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67111303","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 : 2021-06-22DOI: 10.15789/1563-0625-tco-2121
E. Davydova, M. Osikov, K. Abramov
Isolated fractures of femur account for more than 10% of all road traffic injuries. Traumatic injury of femoral bone triggers a cascade of interrelated neuroendocrine reactions at systemic level, primarily at the hypothalamic-pituitary-adrenal axis, systemic response of immune system, initiated by release of tissue degradation products, cytokines and other mediators of damage into systemic blood circulation. Specific cellular reactions in response to traumatic injury to bone tissue include both innate and adaptive immune responses. In this regard, there is still scarce information on changes in blood lymphocyte subpopulations observed after closed isolated fracture of the femoral diaphysis at the middle third, before and after surgery. The aim of the present study was to evaluate the subpopulations of peripheral blood lymphocytes following closed isolated fracture of the femoral diaphysis with bone displacement in thecourse dynamics of surgical treatment, thus being required for studies in pathogenesis, development of diagnostic criteria and creating innovative treatment approaches. The study included 20 apparently healthy men and 36 men with closed isolated fracture of the femoral diaphysis of the middle third (32A and 32B, by AO/ASIF clinical classification, coded according to ICD-10 S72.3). The exclusion criteria were as follows: exacerbation of chronic comorbidities, diseases of lymphatic system and haematopoietic organs, oncological diseases, and evidence of osteoporosis. The spectrum of blood lymphocyte subsets was assessed on days 5, 7 (immediately after surgery) and on day 18 after closed isolated fracture of femoral diaphysis. We have found that, on the day 5 after IPBC along with leukocytosis in peripheral blood, the number of T-regulatory cells, cells with markers of early (CD25+) and late activation (HLA-DR+) proved to be increased, whereas representation of NK cells was decreased. On the day 7 after IPBC and immediately after surgery, leukocytosis persisted in blood, along with increased number of T-regulatory cells, CD3+ cells with early and late activation markers. On the day 18 after closed isolated fracture of the femoral diaphysis, the total numbers of leukocytes, T-lymphocytes, T-helpers, T-regulatory cells, T cells with an early activation marker are restored in peripheral blood, whereas the number of T-lymphocytes expressing HLA-DR+ molecules showed a significant increase.
{"title":"Time course of lymphocyte profile after femoral bone fracture","authors":"E. Davydova, M. Osikov, K. Abramov","doi":"10.15789/1563-0625-tco-2121","DOIUrl":"https://doi.org/10.15789/1563-0625-tco-2121","url":null,"abstract":"Isolated fractures of femur account for more than 10% of all road traffic injuries. Traumatic injury of femoral bone triggers a cascade of interrelated neuroendocrine reactions at systemic level, primarily at the hypothalamic-pituitary-adrenal axis, systemic response of immune system, initiated by release of tissue degradation products, cytokines and other mediators of damage into systemic blood circulation. Specific cellular reactions in response to traumatic injury to bone tissue include both innate and adaptive immune responses. In this regard, there is still scarce information on changes in blood lymphocyte subpopulations observed after closed isolated fracture of the femoral diaphysis at the middle third, before and after surgery. The aim of the present study was to evaluate the subpopulations of peripheral blood lymphocytes following closed isolated fracture of the femoral diaphysis with bone displacement in thecourse dynamics of surgical treatment, thus being required for studies in pathogenesis, development of diagnostic criteria and creating innovative treatment approaches. The study included 20 apparently healthy men and 36 men with closed isolated fracture of the femoral diaphysis of the middle third (32A and 32B, by AO/ASIF clinical classification, coded according to ICD-10 S72.3). The exclusion criteria were as follows: exacerbation of chronic comorbidities, diseases of lymphatic system and haematopoietic organs, oncological diseases, and evidence of osteoporosis. The spectrum of blood lymphocyte subsets was assessed on days 5, 7 (immediately after surgery) and on day 18 after closed isolated fracture of femoral diaphysis. We have found that, on the day 5 after IPBC along with leukocytosis in peripheral blood, the number of T-regulatory cells, cells with markers of early (CD25+) and late activation (HLA-DR+) proved to be increased, whereas representation of NK cells was decreased. On the day 7 after IPBC and immediately after surgery, leukocytosis persisted in blood, along with increased number of T-regulatory cells, CD3+ cells with early and late activation markers. On the day 18 after closed isolated fracture of the femoral diaphysis, the total numbers of leukocytes, T-lymphocytes, T-helpers, T-regulatory cells, T cells with an early activation marker are restored in peripheral blood, whereas the number of T-lymphocytes expressing HLA-DR+ molecules showed a significant increase.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67112130","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 : 2021-06-22DOI: 10.15789/1563-0625-bat-2174
N. Bychkova
Diagnostics of allergic diseases is a difficult issue, which requires distinct solutions, since this disorder is very common among the population. The overview focuses on complex diagnostics, including various methods that are most in demand at the present stage. The allergy diagnostics primarily include taking anamnesis, physical examination, instrumental and functional tests. Less often, the provocative tests are used, due to risk of severe adverse reactions. At the present stage, the role of laboratory diagnostics of allergies is growing, since, firstly, there is an increase in difficult-to-diagnose cases that require involvement of the entire medical armamentarium, and, secondly, the sensitivity and specificity of laboratory tests are improving. Among laboratory methods, the most significant are the assessment of the level of specific IgE, and the relatively new basophile activation test. The latter test is the main focus of the present review. It is functional and combines the advantages of provocative tests, during which conditions are created for the interaction of a potential allergen and effector cells of allergic inflammation, keeping safety for the patient. The data on the life cycle of basophils, their expression of membrane receptors, the content of granules, and ability to produce additional inflammatory mediators by the cells are presented. Participation of these cells in pathogenesis of allergic inflammation is being considered. Various mechanisms of basophil activation are discussed, both IgE-mediated and IgE-independent, which are similar in vivo and in vitro. Theoretical aspects of using the in vitro basophil activation test to estimate the hypersensitivity to a wide range of allergens are discussed. High sensitivity and specificity of the test for diagnosing allergies to food, household, pollen, insect and drug allergens are presented. Specific features of the basophil activation test related to the preanalytical, analytical and postanalytical stages of the study are highlighted. The factors influencing evaluation of this method are known. For example, difficulties in interpreting the test may arise while taking glucocorticosteroid hormones, in acute period of inflammation, with severe edema. The possibility of using this test to assess effectiveness of allergen-specific and anti-IgE therapy is being considered. A comparison of the basophil activation test, measurement of specific IgE and skin tests by various parameters related to performance and interpretation of results is carried out. Comprehensive diagnostics of allergic diseases, including usage of pathogenetically determined laboratory methods, will contribute to adequate treatment and, as a result, improve the health of the population.
{"title":"Basophil activation: theoretical aspects and use in the diagnosis of allergic diseases","authors":"N. Bychkova","doi":"10.15789/1563-0625-bat-2174","DOIUrl":"https://doi.org/10.15789/1563-0625-bat-2174","url":null,"abstract":"Diagnostics of allergic diseases is a difficult issue, which requires distinct solutions, since this disorder is very common among the population. The overview focuses on complex diagnostics, including various methods that are most in demand at the present stage. The allergy diagnostics primarily include taking anamnesis, physical examination, instrumental and functional tests. Less often, the provocative tests are used, due to risk of severe adverse reactions. At the present stage, the role of laboratory diagnostics of allergies is growing, since, firstly, there is an increase in difficult-to-diagnose cases that require involvement of the entire medical armamentarium, and, secondly, the sensitivity and specificity of laboratory tests are improving. Among laboratory methods, the most significant are the assessment of the level of specific IgE, and the relatively new basophile activation test. The latter test is the main focus of the present review. It is functional and combines the advantages of provocative tests, during which conditions are created for the interaction of a potential allergen and effector cells of allergic inflammation, keeping safety for the patient. The data on the life cycle of basophils, their expression of membrane receptors, the content of granules, and ability to produce additional inflammatory mediators by the cells are presented. Participation of these cells in pathogenesis of allergic inflammation is being considered. Various mechanisms of basophil activation are discussed, both IgE-mediated and IgE-independent, which are similar in vivo and in vitro. Theoretical aspects of using the in vitro basophil activation test to estimate the hypersensitivity to a wide range of allergens are discussed. High sensitivity and specificity of the test for diagnosing allergies to food, household, pollen, insect and drug allergens are presented. Specific features of the basophil activation test related to the preanalytical, analytical and postanalytical stages of the study are highlighted. The factors influencing evaluation of this method are known. For example, difficulties in interpreting the test may arise while taking glucocorticosteroid hormones, in acute period of inflammation, with severe edema. The possibility of using this test to assess effectiveness of allergen-specific and anti-IgE therapy is being considered. A comparison of the basophil activation test, measurement of specific IgE and skin tests by various parameters related to performance and interpretation of results is carried out. Comprehensive diagnostics of allergic diseases, including usage of pathogenetically determined laboratory methods, will contribute to adequate treatment and, as a result, improve the health of the population.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67108382","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 : 2021-06-22DOI: 10.15789/1563-0625-ceo-2118
S. Suprun, N. Kuderova, E. Suprun, O. Morozova, G. Evseeva, O. Lebedko
Inflammation is among the factors promoting development of premature rupture of the membranes (PPROM). Upon the conditions of physiological immune imbalance in pregnancy, inflammation modifies its course and can even change the immune response. Appropriate indexes may be quantitative and functional. We used a marker of mitochondrial membrane potential (MPM, Ay) as an integral index of the functional state of immunocompetent blood cells (IBC) in 159 women who were examined at 8-14 weeks of gestation; they were observed up to 34-36 weeks. Of these cohort, 121 women were referred to a comparison group. The main group (n = 46) consisted of pregnant women with PPROM at the term of 28-33 weeks. The examination was carried out according to current medical standards, with informed consent, being approved by the Ethics committee at the Khabarovsk branch of Far Eastern Scientific Centre of Physiology and Pathology of Respiration — Research Institute of Maternity and Childhood Protection. Additionally, MPM and lymphocyte populations were determined by flow cytometry. The degree of disturbed energy supply in the IBC was based on the data of simultaneous determination of lymphocyte, granulocyte and monocyte numbers with reduced MPM values (application for invention No. 2020115963), thus revealing 3 degrees of energy deficiency: 1 st degree, monovariant IBC composition with reduced MPM; 2 nd degree, bivariant composition, 3 rd degree, total changes. A relative and absolute decrease in CD3 (72% vs 78% and 1624 vs 1980), CD8 (28% vs 33% and 651 vs 851), an increase in CD19 (14% vs 9% and 304 vs 219) were revealed in pregnant women with PPROM. When assessing MPM values in the IBC populations, a decreased proportion of women without energy deficiency from the 1 st to the 2 nd trimester (from 41% to 30%), due to the 3 rd degree of energy deficiency (from 17% to 26%) was detected. A shift of affected pools at the 2 nd degree of energy deficiency in favor of lymphocytic-granulocytic association (from 7% to 25%) from lymphocytic-monocytic compartment (from 73% to 50%) was found. From the 2nd to 3rd trimester, we have detected redistribution of granulocyte pools at the 1 st degree (0 to 8%) and from the lymphocytic-granulocytic association (25% and 5%) to monocytic-granulocytic (25% and 40%). In the group with PPROM, there was a decreased proportion of pregnant women without energy deficiency (13% and 27%), as well as with the 1 st and 2 nd degrees (17% vs 31% and 9% vs 17%), due to the 3 rd degree of energy deficiency (61% and 26 %), relative to the comparison group. The IBC pools of in the main group were redistributed at the 1 st degree in favor of granulocytes (25% and 8%), at the 2 nd , in favor of the lymphocytic-monocytic association (100% and 55%) from the granulocytic-monocytic (0% and 40%). Such imbalance of bioenergetic processes in the IBC can be an important factor of pathologically ongoing inflammation. These changes could be caused by both higher inciden
炎症是促进胎膜早破(PPROM)发展的因素之一。在妊娠期生理免疫失衡的情况下，炎症改变其进程，甚至可以改变免疫反应。适当的指标可以是定量的和功能性的。我们使用线粒体膜电位标记物(MPM, Ay)作为衡量159名妊娠8-14周妇女免疫活性血细胞(IBC)功能状态的综合指标;观察至34-36周。在这些队列中，121名妇女被转介到对照组。主要组(n = 46)为28-33周PPROM孕妇。检查是在知情同意的情况下，按照现行医疗标准进行的，并得到远东呼吸生理学和病理学科学中心-妇幼保护研究所哈巴罗夫斯克分院伦理委员会的批准。此外，流式细胞术检测MPM和淋巴细胞群。IBC能量供应紊乱程度是基于MPM值降低的淋巴细胞、粒细胞和单核细胞数量同时测定的数据(申请发明号2020115963)，从而揭示出3个程度的能量不足:1度，单变IBC组成，MPM降低;二度，双变成分，三度，总变化。PPROM孕妇CD3 (72% vs 78%， 1624 vs 1980)， CD8 (28% vs 33%， 651 vs 851)， CD19 (14% vs 9%， 304 vs 219)的相对和绝对下降。当评估IBC人群的MPM值时，发现由于第三度能量缺乏(从17%到26%)，从妊娠1至2个月无能量缺乏的妇女比例下降(从41%到30%)。发现受影响的池在二级能量缺乏时有利于淋巴细胞-粒细胞关联(从7%到25%)，从淋巴细胞-单核细胞室(从73%到50%)。从妊娠2 - 3个月，我们发现粒细胞池的重新分布在1级(0 - 8%)，从淋巴细胞-粒细胞关联(25%和5%)到单核细胞-粒细胞关联(25%和40%)。在PPROM组中，由于3度能量缺乏(61%和26%)，与对照组相比，无能量缺乏的孕妇比例(13%和27%)以及1度和2度(17%对31%和9%对17%)的孕妇比例有所下降。主组的IBC池在第1度重新分布，有利于粒细胞(25%和8%)，在第2度，有利于淋巴细胞-单核细胞的关联(100%和55%)，而不是粒细胞-单核细胞(0%和40%)。IBC中这种生物能量过程的不平衡可能是病理性持续炎症的重要因素。这些变化可能是由这类患者较高的感染发生率和母亲与胎儿之间的同种免疫相互作用引起的。然而，它们也可能决定炎症的病理过程。早产通常是由PPROM引起的，是一种多因素的病理状况。然而，独立于特定的触发因素，至少IBC能量供应的变化可以作为该疾病可能性的重要生物标志物。
{"title":"Complex estimation of mitochondrial changes of immunocompetent blood cells in pregnant women with urgent and premature birth","authors":"S. Suprun, N. Kuderova, E. Suprun, O. Morozova, G. Evseeva, O. Lebedko","doi":"10.15789/1563-0625-ceo-2118","DOIUrl":"https://doi.org/10.15789/1563-0625-ceo-2118","url":null,"abstract":"Inflammation is among the factors promoting development of premature rupture of the membranes (PPROM). Upon the conditions of physiological immune imbalance in pregnancy, inflammation modifies its course and can even change the immune response. Appropriate indexes may be quantitative and functional. We used a marker of mitochondrial membrane potential (MPM, Ay) as an integral index of the functional state of immunocompetent blood cells (IBC) in 159 women who were examined at 8-14 weeks of gestation; they were observed up to 34-36 weeks. Of these cohort, 121 women were referred to a comparison group. The main group (n = 46) consisted of pregnant women with PPROM at the term of 28-33 weeks. The examination was carried out according to current medical standards, with informed consent, being approved by the Ethics committee at the Khabarovsk branch of Far Eastern Scientific Centre of Physiology and Pathology of Respiration — Research Institute of Maternity and Childhood Protection. Additionally, MPM and lymphocyte populations were determined by flow cytometry. The degree of disturbed energy supply in the IBC was based on the data of simultaneous determination of lymphocyte, granulocyte and monocyte numbers with reduced MPM values (application for invention No. 2020115963), thus revealing 3 degrees of energy deficiency: 1 st degree, monovariant IBC composition with reduced MPM; 2 nd degree, bivariant composition, 3 rd degree, total changes. A relative and absolute decrease in CD3 (72% vs 78% and 1624 vs 1980), CD8 (28% vs 33% and 651 vs 851), an increase in CD19 (14% vs 9% and 304 vs 219) were revealed in pregnant women with PPROM. When assessing MPM values in the IBC populations, a decreased proportion of women without energy deficiency from the 1 st to the 2 nd trimester (from 41% to 30%), due to the 3 rd degree of energy deficiency (from 17% to 26%) was detected. A shift of affected pools at the 2 nd degree of energy deficiency in favor of lymphocytic-granulocytic association (from 7% to 25%) from lymphocytic-monocytic compartment (from 73% to 50%) was found. From the 2nd to 3rd trimester, we have detected redistribution of granulocyte pools at the 1 st degree (0 to 8%) and from the lymphocytic-granulocytic association (25% and 5%) to monocytic-granulocytic (25% and 40%). In the group with PPROM, there was a decreased proportion of pregnant women without energy deficiency (13% and 27%), as well as with the 1 st and 2 nd degrees (17% vs 31% and 9% vs 17%), due to the 3 rd degree of energy deficiency (61% and 26 %), relative to the comparison group. The IBC pools of in the main group were redistributed at the 1 st degree in favor of granulocytes (25% and 8%), at the 2 nd , in favor of the lymphocytic-monocytic association (100% and 55%) from the granulocytic-monocytic (0% and 40%). Such imbalance of bioenergetic processes in the IBC can be an important factor of pathologically ongoing inflammation. These changes could be caused by both higher inciden","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67108603","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 : 2021-06-22DOI: 10.15789/1563-0625-doa-2169
A. Kudryashova, A. Borisov, A. Koltsova, A. Pushkina, O. Borisova
Our aim was to compare different immobilized erythropoietin (EPO) preparations for their ability to detect anti-EPO IgG antibodies in blood sera of EPO-treated patients with ELISA technique. 294 serum samples of the patients treated with erythropoietin were analyzed. 127 serum samples of patients who did not receive recombinant human EPO (rhEPO) were studied for comparative analysis. ELISA assay was performed, and different rhEPO drugs were immobilized on the anti-EPO monoclonal antibody-coated plates. Horseradish peroxidase-conjugated mouse monoclonal antibodies to human IgG, IgG1, and IgG4 was used for detection. The following drugs were studied: recombinant human erythropoietin rhEPO-beta (Shandong Kexing Bioproducts), European standard of erythropoietin BRP 3, commercial drugs Aranesp (Amgen Europe B.V.), Mircera (F. Hoffmann-La Roche Ltd.), Eprex (Johnson & Johnson LLC), Eralfon (Pharmaceutical Company Sotex). The sensitivity of the method was expressed as a positivity index (IP). IP calculated as the ratio of OD from tested sera to OD at the cut-off levels. The latter was assumed as a mean OD±SD for serum samples from EPO-naive patients. The results were evaluated as positive with IP > 1.1, and negative at IP < 0.9. Results in the range of 0.9 ≤ IP < 1.1 were considered as unidentified. Among the 294 samples, 32 specimens were evaluated as positive or unidentified for total IgG anti-EPO antibodies. The unidentified samples were detected in 1.0-1.7% of all cases. IgG1 subclass antibodies were found in 50-56.3% of patients and IgG4 subclass antibodies, in 43.850% of the patients. Mann—Whitney test showed a significant difference between the test samples compared to control group for all the ELISA modifications (p = 0.001). The Kruskal—Wallis test did not show significant differences between the IP results obtained with any of five immobilized EPO drugs (p = 0.05). The correlation quotient of IP was in the range of 0.99-0.96 for total IgG and > 0.98 for two subclasses of antibodies. Linear regression coefficients were close to one, thus indicating absence of significant differences in the sensitivity of the compared methods. This study indicate the opportunity of using the similar test systems to determine anti-EPO antibodies in the patients treated with various rhEPO drugs. Therefore, it is possible to develop a universal commercial test system to this purpose.
{"title":"Detection of antibodies to erythropoietin-based drugs: is it possible to create the universal test system?","authors":"A. Kudryashova, A. Borisov, A. Koltsova, A. Pushkina, O. Borisova","doi":"10.15789/1563-0625-doa-2169","DOIUrl":"https://doi.org/10.15789/1563-0625-doa-2169","url":null,"abstract":"Our aim was to compare different immobilized erythropoietin (EPO) preparations for their ability to detect anti-EPO IgG antibodies in blood sera of EPO-treated patients with ELISA technique. 294 serum samples of the patients treated with erythropoietin were analyzed. 127 serum samples of patients who did not receive recombinant human EPO (rhEPO) were studied for comparative analysis. ELISA assay was performed, and different rhEPO drugs were immobilized on the anti-EPO monoclonal antibody-coated plates. Horseradish peroxidase-conjugated mouse monoclonal antibodies to human IgG, IgG1, and IgG4 was used for detection. The following drugs were studied: recombinant human erythropoietin rhEPO-beta (Shandong Kexing Bioproducts), European standard of erythropoietin BRP 3, commercial drugs Aranesp (Amgen Europe B.V.), Mircera (F. Hoffmann-La Roche Ltd.), Eprex (Johnson & Johnson LLC), Eralfon (Pharmaceutical Company Sotex). The sensitivity of the method was expressed as a positivity index (IP). IP calculated as the ratio of OD from tested sera to OD at the cut-off levels. The latter was assumed as a mean OD±SD for serum samples from EPO-naive patients. The results were evaluated as positive with IP > 1.1, and negative at IP < 0.9. Results in the range of 0.9 ≤ IP < 1.1 were considered as unidentified. Among the 294 samples, 32 specimens were evaluated as positive or unidentified for total IgG anti-EPO antibodies. The unidentified samples were detected in 1.0-1.7% of all cases. IgG1 subclass antibodies were found in 50-56.3% of patients and IgG4 subclass antibodies, in 43.850% of the patients. Mann—Whitney test showed a significant difference between the test samples compared to control group for all the ELISA modifications (p = 0.001). The Kruskal—Wallis test did not show significant differences between the IP results obtained with any of five immobilized EPO drugs (p = 0.05). The correlation quotient of IP was in the range of 0.99-0.96 for total IgG and > 0.98 for two subclasses of antibodies. Linear regression coefficients were close to one, thus indicating absence of significant differences in the sensitivity of the compared methods. This study indicate the opportunity of using the similar test systems to determine anti-EPO antibodies in the patients treated with various rhEPO drugs. Therefore, it is possible to develop a universal commercial test system to this purpose.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67109249","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 : 2021-06-22DOI: 10.15789/1563-0625-ieo-2205
L. Sizyakina, I. I. Andrreeva, A. I. Sergeeva
Rapid progression of aesthetic medicine is a distinctive feature of present decade. In this area, leading position is taken by injection cosmetology, which is associated with an opportunity of pathogenetic approach to resolution of cosmetic problems primarily caused by skin aging. The most commonly used mesotherapy drugs, along with hyaluronic acid, are vitamins, amino acids, and microelements. Skin aging is associated with quantitative and functional changes in the local immune cell populations. In this case, it is rational to assume distinct effects of peptide complexes upon functional potential of immunocompetent cells. The aim of this study was to analyze time-dependent changes of some immune parameters after mesotherapy with a complex of hyaluronic acid and peptides. The observation group consisted of 26 women who received their course of mesotherapy for the first time. Objective instrumental evaluation of the effect with Aramo Smart Lite device showed that, after mesotherapy, the skin quality was significantly improving in comparison with pre-treatment conditions, due to decreased relief of skin creases and wrinkles, with a tendency for reduction of this effect six months later. When comparing the results of immunological testing in the patients after the course of treatment with the data before starting the therapy, we have found redistribution in the lymphoid cell populations, i.e., increased proportion of T-lymphocytes, decreased amounts of B cells, and CD16+ natural killers. Declined numbers of T-lymphocytes expressing early activation marker were associated with increased proportion of peripheral Treg lymphocytes. We have also detected activation of antibody production which manifested as increased levels of all major classes of serum immunoglobulins. Enhanced spontaneous oxidative activity of neutrophils was also noted. The results of immunological monitoring showed that, three months post-treatment, none of the quantitative and functional parameters of immunity was changed, as compared with the results obtained immediately after ending the mesotherapy. Six months later, however, all these indexes returned to their initial positions assessed before the cosmetic procedure. The changes in systemic immune response following mesotherapy with peptide complexes affect the mechanisms of both innate and acquired immunity, including differentiation of lymphocytes, their regulatory functions and activation potential, and provide modulation of effector reactions. Complete restoration of initial immune parameters is observed within six months.
{"title":"Immunotropic effects of mesotherapy used for correction of age-related skin changes","authors":"L. Sizyakina, I. I. Andrreeva, A. I. Sergeeva","doi":"10.15789/1563-0625-ieo-2205","DOIUrl":"https://doi.org/10.15789/1563-0625-ieo-2205","url":null,"abstract":"Rapid progression of aesthetic medicine is a distinctive feature of present decade. In this area, leading position is taken by injection cosmetology, which is associated with an opportunity of pathogenetic approach to resolution of cosmetic problems primarily caused by skin aging. The most commonly used mesotherapy drugs, along with hyaluronic acid, are vitamins, amino acids, and microelements. Skin aging is associated with quantitative and functional changes in the local immune cell populations. In this case, it is rational to assume distinct effects of peptide complexes upon functional potential of immunocompetent cells. The aim of this study was to analyze time-dependent changes of some immune parameters after mesotherapy with a complex of hyaluronic acid and peptides. The observation group consisted of 26 women who received their course of mesotherapy for the first time. Objective instrumental evaluation of the effect with Aramo Smart Lite device showed that, after mesotherapy, the skin quality was significantly improving in comparison with pre-treatment conditions, due to decreased relief of skin creases and wrinkles, with a tendency for reduction of this effect six months later. When comparing the results of immunological testing in the patients after the course of treatment with the data before starting the therapy, we have found redistribution in the lymphoid cell populations, i.e., increased proportion of T-lymphocytes, decreased amounts of B cells, and CD16+ natural killers. Declined numbers of T-lymphocytes expressing early activation marker were associated with increased proportion of peripheral Treg lymphocytes. We have also detected activation of antibody production which manifested as increased levels of all major classes of serum immunoglobulins. Enhanced spontaneous oxidative activity of neutrophils was also noted. The results of immunological monitoring showed that, three months post-treatment, none of the quantitative and functional parameters of immunity was changed, as compared with the results obtained immediately after ending the mesotherapy. Six months later, however, all these indexes returned to their initial positions assessed before the cosmetic procedure. The changes in systemic immune response following mesotherapy with peptide complexes affect the mechanisms of both innate and acquired immunity, including differentiation of lymphocytes, their regulatory functions and activation potential, and provide modulation of effector reactions. Complete restoration of initial immune parameters is observed within six months.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67109537","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 : 2021-06-22DOI: 10.15789/1563-0625-sis-2230
M. E. Malyshev, A. K. Iordanishvili, P. A. Mushegyan, T. G. Khabirova
Age-related changes in the oral mucosa immunity, including decreased contents of secretory immunoglobulins and antimicrobial peptides in saliva, along with changed balance of pro- and antiinflammatory cytokines, care risks for development of purulent-inflammatory or allergic diseases of the oral cavity. For example, denture stomatitis (DS) caused by Candida albicans occurs in about 30—70% of denture users. The purpose of this study was to assess the secretory immune state of oral mucous membranes in the patients with Candida-associated denture stomatitis. We examined 42 elderly patients (61-72 years old) with one-piece acrylic dentures for at least, 6 months (15 men and 27 women). Based on clinical and microbiological studies, the patients were divided into a group with DS (n = 24) and a group without DS (n = 18). The contents of secretory immunoglobulin A (sIgA) and proinflammatory cytokines was determined, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as antimicrobial peptides (cathelicidin LL-37, lactoferrin and alphadefensins 1-3 (HNP1-3). The sIgA levels in the salivary fluid of patients with DS (0.92 (0.80-1.26) g/l) were significantly lower (p < 0.05) than in patients without stomatitis (1.71 (1.23-2,13) g/l). In the group with advanced DS, a significant increase of IL-1β levels in saliva was observed, along with simultaneous decrease of IL-8 concentrations, compared to the other group, without differences in TNFα and IL-6 concentrations. Increased contents of IL-10 in saliva was also noted. It was shown that the concentrations of cathelicidin LL-37 in saliva of the DS patients was increased two-fold, whereas the contents of neutrophil-derived alpha-defensins (HNP 1-3) was decreased. Conclusions: The development of inflammation in denture stomatitis caused by usage of removable acrylic dentures associated with Candida albicans infection is characterized by functional insufficiency of the secretory immunity of the oral mucosa associated with decreased amounts of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin. Low levels of alpha-defensins may suggest a decrease in the functional activity of neutrophils in the elderly, thus leading to higher susceptibility to fungal infection of oral cavity.
{"title":"Secretory immune status of oral cavity in the patients with Сandida-associated denture stomatitis","authors":"M. E. Malyshev, A. K. Iordanishvili, P. A. Mushegyan, T. G. Khabirova","doi":"10.15789/1563-0625-sis-2230","DOIUrl":"https://doi.org/10.15789/1563-0625-sis-2230","url":null,"abstract":"Age-related changes in the oral mucosa immunity, including decreased contents of secretory immunoglobulins and antimicrobial peptides in saliva, along with changed balance of pro- and antiinflammatory cytokines, care risks for development of purulent-inflammatory or allergic diseases of the oral cavity. For example, denture stomatitis (DS) caused by Candida albicans occurs in about 30—70% of denture users. The purpose of this study was to assess the secretory immune state of oral mucous membranes in the patients with Candida-associated denture stomatitis. We examined 42 elderly patients (61-72 years old) with one-piece acrylic dentures for at least, 6 months (15 men and 27 women). Based on clinical and microbiological studies, the patients were divided into a group with DS (n = 24) and a group without DS (n = 18). The contents of secretory immunoglobulin A (sIgA) and proinflammatory cytokines was determined, i.e., interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNFα), and anti-inflammatory cytokines, e.g., receptor antagonist of interleukin-1 (RAIL), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as antimicrobial peptides (cathelicidin LL-37, lactoferrin and alphadefensins 1-3 (HNP1-3). The sIgA levels in the salivary fluid of patients with DS (0.92 (0.80-1.26) g/l) were significantly lower (p < 0.05) than in patients without stomatitis (1.71 (1.23-2,13) g/l). In the group with advanced DS, a significant increase of IL-1β levels in saliva was observed, along with simultaneous decrease of IL-8 concentrations, compared to the other group, without differences in TNFα and IL-6 concentrations. Increased contents of IL-10 in saliva was also noted. It was shown that the concentrations of cathelicidin LL-37 in saliva of the DS patients was increased two-fold, whereas the contents of neutrophil-derived alpha-defensins (HNP 1-3) was decreased. Conclusions: The development of inflammation in denture stomatitis caused by usage of removable acrylic dentures associated with Candida albicans infection is characterized by functional insufficiency of the secretory immunity of the oral mucosa associated with decreased amounts of secretory immunoglobulin A and antimicrobial peptides of neutrophilic origin. Low levels of alpha-defensins may suggest a decrease in the functional activity of neutrophils in the elderly, thus leading to higher susceptibility to fungal infection of oral cavity.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67111858","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 : 2021-06-22DOI: 10.15789/1563-0625-HDI-2182
E. Khamaganova, E. Leonov, A. Abdrakhimova, S. Khizhinskiy, T. Gaponova, V. Savchenko
Next generation sequencing is used to determine full-length sequences of HLA genes at the 4-field (allelic) resolution. The study was aimed at determining frequency and diversity of HLA alleles in a cohort of blood donors from the Registry of the National Research Center for Hematology who design ated themselves as Russians (including some not routinely typed variations in HLA gene regions). The studied population consisted of 1510 donors. HLA typing was performed by next generation sequencing. Libraries were performed with AllType NGS Amplification Kits (One Lambda, USA) and sequenced using MiSeq (Illumina, USA). Data analysis used the TypeStream Visual Software V2.0.0.68 (One Lambda, USA) and IPD-IMGT/HLA database 3.40.0.1. Arlequin 3.5 software was used for estimation of allele and haplotype frequencies, deviation from Hardy-Weinberg equilibrium. 82 HLA-A, 156 HLA-В and 85 HLA-С alleles were identified with four-field resolution. 45 HLA-DRB1 and 18 HLA-DQB1 alleles were identified with 2-3-field resolution. Considerable HLA diversity was found among the donors self-designated as Russians: the population had large numbers of distinct alleles at each HLA gene, high percentage of alleles (25-32% of HLA class I) were revealed only once. Sufficient numbers of new alleles were registered which are absent in the IPD-IMGT/HLA database. Considerable allelic diversity in Russian population is due to low-incidence alleles. Despite this diversity, the majority of HLA alleles detected at each locus were common. Significant HLA diversity of the donors was connected with a large number of alleles with rare occurrence. The novel alleles identified in our study differed from the known alleles by single nucleotide substitutions. The most common alleles at the four-field level were as follows: A*02:01:01:01 (27.1%), C*07:02:01:03 (13.1%), A*03:01:01:01 (13.0%), B*07:02:01:01 (13.0%), A*01:01:01:01 (11.6%) and C*07:01:01:01/16 (10.4%). The HLA alleles, which are common for Russian populations, are not always common or well-documented alleles in present catalogues. The data obtained in this study may be used as a reference sample for estimation of HLA allele frequencies in Russian population, for proper frequency evaluation of specific alleles when searching donors for allogeneic hematopoietic stem cell transplantation, as well as for association studies between HLA alleles and different diseases, and for research in population genetics.
{"title":"HLA diversity in the Russian population assessed by next generation sequencing","authors":"E. Khamaganova, E. Leonov, A. Abdrakhimova, S. Khizhinskiy, T. Gaponova, V. Savchenko","doi":"10.15789/1563-0625-HDI-2182","DOIUrl":"https://doi.org/10.15789/1563-0625-HDI-2182","url":null,"abstract":"Next generation sequencing is used to determine full-length sequences of HLA genes at the 4-field (allelic) resolution. The study was aimed at determining frequency and diversity of HLA alleles in a cohort of blood donors from the Registry of the National Research Center for Hematology who design ated themselves as Russians (including some not routinely typed variations in HLA gene regions). The studied population consisted of 1510 donors. HLA typing was performed by next generation sequencing. Libraries were performed with AllType NGS Amplification Kits (One Lambda, USA) and sequenced using MiSeq (Illumina, USA). Data analysis used the TypeStream Visual Software V2.0.0.68 (One Lambda, USA) and IPD-IMGT/HLA database 3.40.0.1. Arlequin 3.5 software was used for estimation of allele and haplotype frequencies, deviation from Hardy-Weinberg equilibrium. 82 HLA-A, 156 HLA-В and 85 HLA-С alleles were identified with four-field resolution. 45 HLA-DRB1 and 18 HLA-DQB1 alleles were identified with 2-3-field resolution. Considerable HLA diversity was found among the donors self-designated as Russians: the population had large numbers of distinct alleles at each HLA gene, high percentage of alleles (25-32% of HLA class I) were revealed only once. Sufficient numbers of new alleles were registered which are absent in the IPD-IMGT/HLA database. Considerable allelic diversity in Russian population is due to low-incidence alleles. Despite this diversity, the majority of HLA alleles detected at each locus were common. Significant HLA diversity of the donors was connected with a large number of alleles with rare occurrence. The novel alleles identified in our study differed from the known alleles by single nucleotide substitutions. The most common alleles at the four-field level were as follows: A*02:01:01:01 (27.1%), C*07:02:01:03 (13.1%), A*03:01:01:01 (13.0%), B*07:02:01:01 (13.0%), A*01:01:01:01 (11.6%) and C*07:01:01:01/16 (10.4%). The HLA alleles, which are common for Russian populations, are not always common or well-documented alleles in present catalogues. The data obtained in this study may be used as a reference sample for estimation of HLA allele frequencies in Russian population, for proper frequency evaluation of specific alleles when searching donors for allogeneic hematopoietic stem cell transplantation, as well as for association studies between HLA alleles and different diseases, and for research in population genetics.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"23 1","pages":"509-522"},"PeriodicalIF":0.0,"publicationDate":"2021-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46229235","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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