Pub Date : 2021-01-10DOI: 10.15789/1563-0625-nod-2101
A. Eissa, O. Rasslan, Lamia Fouad, Fahim Hisham Abdelmajeed, Amira Esmail Abdel-Hamid
Bladder cancer is the 7th most commonly diagnosed cancer in males worldwide and the 11th when both genders are considered. Seventy five per cent of bladder cancer cases are non-muscle invasive bladder cancer (NMIBC). Bacillus Calmette–Gu rin (BCG) immunotherapy remains the standard intravesical agent for NMIBC. The exact mechanism by which BCG prevents recurrence is unknown. The aim of this study was to evaluate NLR4 gene expression and IL-1β as possible prognostic indicators for NMIBC recurrence and BCG treatment failure, and to detect the difference in their levels among muscle invasive bladder cancer (MIBC) and NMIBC that may aid in primary differentiation between cases. This study was conducted in 30 patients who had NMIBC and 17 patients who had MIBC. Urine samples were obtained in sterile cups before operation. From NMIBC cases, four more samples were obtained as mentioned below. Evaluation of NLR4 gene expression was performed in pre-surgical sample for MIBC and in 4 samples for NMIBC: pre-surgical sample, sample collected 4 hours after the 3rd dose of BCG instillation, and samples collected during follow up (3 and 6 months post-surgically). There was statistical significant increase in NLRP4 expression levels in NMIBC (CT=0.87±1.48) compared to MIBC (CT=2.82±2.07). As far as we searched, no published results were found regarding comparative gene expression levels between NMIBC and MIBC cases. Gene expression in recurrent cases was higher in pre-surgical urine samples than in non-recurrent cases. The expression level further increased up to 21 fold than the pre-surgical level in the sample taken after injection of the 3rd dose of BCG. This level decreased distinctly to become 1-fold increase over pre-surgical level at the 3rd month follow up then to only 0.9-fold at the 6th month. In non- recurrent cases, gene expression level started pre-surgically in much lower levels than those encountered in recurrent cases. There were 11-fold increase in expression level after 3rd dose of BCG instillation and then decreased to be 5.6 folds higher in the sample taken at 3rd month follow up than in presurgical samples. Gene expression further decreased to become 4.1 fold higher in samples taken at 6 month follow up than the pre-surgical levels. IL-1β levels were estimated for NMIBC and MIBC cases in urine samples pre-surgically and during BCG therapy in case of NMIBC before and 4 hours after the 3rd dose and during 3rd month follow-up of those cases for searching its possible use of for primary differentiation between NMIBC and MIBC, and also as a prognostic factor for possible recurrence in case of NMIBC cases. The level of IL-1β was generally higher in pre-surgical samples (0.62±0.12 pg/ml) when compared to its level before the 3rd dose of BCG induction therapy (0.53±0.13 pg/ml). Its level was distinctly higher four hours after administration of the 3rd dose BCG (1.96±0.62 pg/ml) than both previous levels. Levels decreased bellow pre-surgical level at
{"title":"Nucleotide Oligomerization Domain-like receptor 4 (NLR4) Gene Expression and Interleukin 1-β (IL 1-β) Level in Urine Samples Before and After Intravesical BCG Therapy For Treatment of Bladder Cancer","authors":"A. Eissa, O. Rasslan, Lamia Fouad, Fahim Hisham Abdelmajeed, Amira Esmail Abdel-Hamid","doi":"10.15789/1563-0625-nod-2101","DOIUrl":"https://doi.org/10.15789/1563-0625-nod-2101","url":null,"abstract":"Bladder cancer is the 7th most commonly diagnosed cancer in males worldwide and the 11th when both genders are considered. Seventy five per cent of bladder cancer cases are non-muscle invasive bladder cancer (NMIBC). Bacillus Calmette–Gu rin (BCG) immunotherapy remains the standard intravesical agent for NMIBC. The exact mechanism by which BCG prevents recurrence is unknown. The aim of this study was to evaluate NLR4 gene expression and IL-1β as possible prognostic indicators for NMIBC recurrence and BCG treatment failure, and to detect the difference in their levels among muscle invasive bladder cancer (MIBC) and NMIBC that may aid in primary differentiation between cases. This study was conducted in 30 patients who had NMIBC and 17 patients who had MIBC. Urine samples were obtained in sterile cups before operation. From NMIBC cases, four more samples were obtained as mentioned below. Evaluation of NLR4 gene expression was performed in pre-surgical sample for MIBC and in 4 samples for NMIBC: pre-surgical sample, sample collected 4 hours after the 3rd dose of BCG instillation, and samples collected during follow up (3 and 6 months post-surgically). There was statistical significant increase in NLRP4 expression levels in NMIBC (CT=0.87±1.48) compared to MIBC (CT=2.82±2.07). As far as we searched, no published results were found regarding comparative gene expression levels between NMIBC and MIBC cases. Gene expression in recurrent cases was higher in pre-surgical urine samples than in non-recurrent cases. The expression level further increased up to 21 fold than the pre-surgical level in the sample taken after injection of the 3rd dose of BCG. This level decreased distinctly to become 1-fold increase over pre-surgical level at the 3rd month follow up then to only 0.9-fold at the 6th month. In non- recurrent cases, gene expression level started pre-surgically in much lower levels than those encountered in recurrent cases. There were 11-fold increase in expression level after 3rd dose of BCG instillation and then decreased to be 5.6 folds higher in the sample taken at 3rd month follow up than in presurgical samples. Gene expression further decreased to become 4.1 fold higher in samples taken at 6 month follow up than the pre-surgical levels. IL-1β levels were estimated for NMIBC and MIBC cases in urine samples pre-surgically and during BCG therapy in case of NMIBC before and 4 hours after the 3rd dose and during 3rd month follow-up of those cases for searching its possible use of for primary differentiation between NMIBC and MIBC, and also as a prognostic factor for possible recurrence in case of NMIBC cases. The level of IL-1β was generally higher in pre-surgical samples (0.62±0.12 pg/ml) when compared to its level before the 3rd dose of BCG induction therapy (0.53±0.13 pg/ml). Its level was distinctly higher four hours after administration of the 3rd dose BCG (1.96±0.62 pg/ml) than both previous levels. Levels decreased bellow pre-surgical level at","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67110760","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 : 2021-01-10DOI: 10.15789/1563-0625-cai-2098
O. Emelyanova, I. Gontar, O. Rusanova, I. Zborovskaya
The study covered 30 apparently healthy individuals and 38 patients with systemic scleroderma. The patients gave their consent to participate in the study in accordance with the World Medical Association Declaration of Helsinki in the current (2013) version (ACR/EULAR). The donors and patients had their blood tested for catalase antibodies with immunoenzyme assay and using magnetic sorbents upon hospital admission and before discharge. It was found that the patients with systemic scleroderma had a reduced oxidase activity of catalase as well as elevated catalase antibodies, compared with the controls. We revealed a statistically significant regularity that the concentration of catalase immunoglobulins is associated with activity and course of the disease. To assess the activity of systemic scleroderma we performed a complex evaluation of two parameters: enzymatic activity and catalase antibody levels. It was established that catalase autoantibodies are mostly revealed in patients with high-activity scleroderma, subacute and acute course of the disease, and when the lungs, skin, kidneys, joints and nervous system were involved, which was conclusively confirmed by a correlation analysis. It is especially important that catalase antibodies should be revealed at early stage of the disease development; they are of especial diagnostic importance, and their changes over time may form the basis for assessing efficiency of administered therapy. The changes in biochemical activity of catalase, elevated antibody titers provide additional criteria of diagnosis in systemic scleroderma. Monitoring of these parameters in hospital settings helps to evaluate the effectiveness of administered therapy and adjust its correction, which is confirmed by inclusion of such extracorporal techniques as plasma separation into the combined treatment schedules. Studying biochemical activity of catalase and formation of catalase antibodies expands our understanding of scleroderma development and opens new avenues for research.
{"title":"Сatalase antibodies in patients with systemic scleroderma as a diagnostic and prognostic marker of the disease","authors":"O. Emelyanova, I. Gontar, O. Rusanova, I. Zborovskaya","doi":"10.15789/1563-0625-cai-2098","DOIUrl":"https://doi.org/10.15789/1563-0625-cai-2098","url":null,"abstract":"The study covered 30 apparently healthy individuals and 38 patients with systemic scleroderma. The patients gave their consent to participate in the study in accordance with the World Medical Association Declaration of Helsinki in the current (2013) version (ACR/EULAR). The donors and patients had their blood tested for catalase antibodies with immunoenzyme assay and using magnetic sorbents upon hospital admission and before discharge. It was found that the patients with systemic scleroderma had a reduced oxidase activity of catalase as well as elevated catalase antibodies, compared with the controls. We revealed a statistically significant regularity that the concentration of catalase immunoglobulins is associated with activity and course of the disease. To assess the activity of systemic scleroderma we performed a complex evaluation of two parameters: enzymatic activity and catalase antibody levels. It was established that catalase autoantibodies are mostly revealed in patients with high-activity scleroderma, subacute and acute course of the disease, and when the lungs, skin, kidneys, joints and nervous system were involved, which was conclusively confirmed by a correlation analysis. It is especially important that catalase antibodies should be revealed at early stage of the disease development; they are of especial diagnostic importance, and their changes over time may form the basis for assessing efficiency of administered therapy. The changes in biochemical activity of catalase, elevated antibody titers provide additional criteria of diagnosis in systemic scleroderma. Monitoring of these parameters in hospital settings helps to evaluate the effectiveness of administered therapy and adjust its correction, which is confirmed by inclusion of such extracorporal techniques as plasma separation into the combined treatment schedules. Studying biochemical activity of catalase and formation of catalase antibodies expands our understanding of scleroderma development and opens new avenues for research.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67108452","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 : 2021-01-10DOI: 10.15789/1563-0625-eop-2093
I. Novikova, Z. V. Zubkova
Platelets are central participants in hemostasis, and also contribute to the host inflammatory and immune responses. Platelets are known to have a direct effect on the formation of neutrophil extracellular traps. Moreover, the patients with systemic lupus erythematosus exhibit multidirectional disturbances in the functional activity of platelets and neutrophils. Changes in inflammatory and thrombotic events can be considered predictors for adverse clinical course in systemic pathology. The aim of present study was to evaluate the possible role of platelets in maintaining increased netosis in patients with systemic lupus erythematosus. Blood platelets and white blood cells from 29 patients with systemic lupus erythematosus (SLE) were subject to the study. We have registered the in vitro effects of platelets upon formation of extracellular traps by autologous neutrophils under the conditions of co-cultivation for 30 minutes (vital NETosis) and 150 minutes (suicidal NETosis), as well as the relationships between the platelet counts, their activity and the number of NETs observed. It was found that the severity and direction of the platelets effect upon NETosis in vitro cultures depends on the degree of activity of disease: in the 1st degree of SLE, the effect of platelets did not differ from healthy individuals, i.e., intact platelets suppress NETosis (p = 0.002), whereas ADP-induced patelets did not exert any effect); at the 2nd degree of activity, both intact and activated platelets increase NETotic activity (p = 0.03 and p = 0.04 for intact and activated platelets, respectively). In the patients with 3rd degree of the disease activity, platelets did not affect formation of NETs. Hyperactivation of platelets was detected in SLE patients, mostly pronounced in the cases with 2nd degree of activity. However, we have not revealed any significant relationships between the count of platelets, their functional activity (according to results of ADP-test aggregation), and the indexes of NETosis. At the same time, the counts of neutrophil extracellular traps in bloodstream depended on the concentration of C-reactive protein (r = 0.58; p = 0.02), the titer of autoantibodies (anti-SS-A and anti-SS-B) (r = 0.66; p = 0.04 and r = 0.76; p = 0.02, respectively), rheumatoid factor (r = 0.73; p = 0.007) and circulating immune complexes (r = 0.68; p = 0.02). The obtained results indicate that the platelet/neutrophil interactions are not the leading cause for increased NETs numbers in SLE, compared to significantly higher effects of soluble autoagressive factors.
{"title":"Effects of platelets on extracellular traps of neutrophils in patients with systemic lupus erythematosus","authors":"I. Novikova, Z. V. Zubkova","doi":"10.15789/1563-0625-eop-2093","DOIUrl":"https://doi.org/10.15789/1563-0625-eop-2093","url":null,"abstract":"Platelets are central participants in hemostasis, and also contribute to the host inflammatory and immune responses. Platelets are known to have a direct effect on the formation of neutrophil extracellular traps. Moreover, the patients with systemic lupus erythematosus exhibit multidirectional disturbances in the functional activity of platelets and neutrophils. Changes in inflammatory and thrombotic events can be considered predictors for adverse clinical course in systemic pathology. The aim of present study was to evaluate the possible role of platelets in maintaining increased netosis in patients with systemic lupus erythematosus. Blood platelets and white blood cells from 29 patients with systemic lupus erythematosus (SLE) were subject to the study. We have registered the in vitro effects of platelets upon formation of extracellular traps by autologous neutrophils under the conditions of co-cultivation for 30 minutes (vital NETosis) and 150 minutes (suicidal NETosis), as well as the relationships between the platelet counts, their activity and the number of NETs observed. It was found that the severity and direction of the platelets effect upon NETosis in vitro cultures depends on the degree of activity of disease: in the 1st degree of SLE, the effect of platelets did not differ from healthy individuals, i.e., intact platelets suppress NETosis (p = 0.002), whereas ADP-induced patelets did not exert any effect); at the 2nd degree of activity, both intact and activated platelets increase NETotic activity (p = 0.03 and p = 0.04 for intact and activated platelets, respectively). In the patients with 3rd degree of the disease activity, platelets did not affect formation of NETs. Hyperactivation of platelets was detected in SLE patients, mostly pronounced in the cases with 2nd degree of activity. However, we have not revealed any significant relationships between the count of platelets, their functional activity (according to results of ADP-test aggregation), and the indexes of NETosis. At the same time, the counts of neutrophil extracellular traps in bloodstream depended on the concentration of C-reactive protein (r = 0.58; p = 0.02), the titer of autoantibodies (anti-SS-A and anti-SS-B) (r = 0.66; p = 0.04 and r = 0.76; p = 0.02, respectively), rheumatoid factor (r = 0.73; p = 0.007) and circulating immune complexes (r = 0.68; p = 0.02). The obtained results indicate that the platelet/neutrophil interactions are not the leading cause for increased NETs numbers in SLE, compared to significantly higher effects of soluble autoagressive factors.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67109486","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 : 2021-01-10DOI: 10.15789/1563-0625-ceo-2072
I. Goldina, E. Markova, I. Orlovskaya, L. Toporkova, V. Kozlov
Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.
{"title":"Corrective effects of original bioflavonoid complex in the cyclophosphamide-induced immunity disorders","authors":"I. Goldina, E. Markova, I. Orlovskaya, L. Toporkova, V. Kozlov","doi":"10.15789/1563-0625-ceo-2072","DOIUrl":"https://doi.org/10.15789/1563-0625-ceo-2072","url":null,"abstract":"Our aim was to evaluate immunomodulatory properties of an original bioflavonoid complex in experimental immune disturbances induced by cyclophosphamide (Cy). We have studied morphometric indexes of thymus and spleen, as well as blood leukocyte counts, cell proliferative activity in lymphoid organs, delayed hypersensitivity responses to T cell-dependent antigen, along with differentiation activity of bone marrow stem cells in experimental animals during Cy-induced immune suppression after a course of bioflavonoid treatment. Suspension of the bioflafonoid complex was introduced to the male mice (СВАхC57Bl/6)F1 aged 12- 14 weeks at a daily dose of 2 mg/animal (80 mg/kg), per os, using gastric catheter, over 14 days. Cytostatic immunosuppression was produced by a single intraperitoneal Cy injection. Proliferative activity of spleen and thymic cells was determined by standard method with Н3 -thymidine incorporation in the 72-h cell culture. Cellular immune response was assayed by the degree of delayed-type hypersensitivity development in response to sheep erythrocytes. The number of hematopoietic progenitors was evaluated by culturing bone marrow cells in methylcellulose-based medium. The experiments have shown mitigation of immunosuppressive effects induced by Cy, in the course of bioflavonoid complex treatment, with respect to absolute and relative mass of lymphoid organs and leukocyte numbers in peripheral blood. Moreover, we have demonstrated decreased effects of Cy treatment upon the spontaneous activity of spleen cells, mitogen-induced thymocyte and splenocyte proliferation, intensivity of delayed-type hypersensitivity response that reached the values of intact animals. Following the course of bioflavonoids, we have revealed an increase in early hematopoietic progenitors. Alleviation of Cy-induced suppressive effects upon cellular immune response, proliferation rates of immune cells, as well as stimulation of hematopoietic stem cell functions suggest a sufficient capacity of the original bioflavonoid complex for modulation of immunity and hematopoiesis, thus presenting experimental proofs for its potential usage as an adjuvant treatment of the patients with malignant diseases.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67108930","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 : 2021-01-10DOI: 10.15789/1563-0625-ppo-2080
M. Zafranskaya, H. Y. Adamovich, A. U. Varabei, A. M. Starastin, D. Nizheharodava
Mechanisms of recognition and effector responses of immune system upon initiation and maintenance of immune-mediated inflammation and tissue damage in inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis (UC), have been actively studied over recent time. Existing evidence suggests these diseases to be caused by abnormal immune response against intestinal flora microorganisms in genetically susceptible individuals. Despite available data on the features of immune disorders in ulcerative colitis and Crohn’s disease, there are still many questions about the involved minor lymphocyte subpopulations and contribution of various functionally active molecules, which play a key role in recognition and initiation of the immune response and can be considered biomarkers of a pathological process in inflammatory bowel diseases. The populations of T lymphocytes with γδT cell receptor, B1 cells and NK T lymphocytes are of greatest interest, as well as functionally active TLRs (Toll-like receptors), CD89, CD314, etc. Due to substantial progress in studying the nature of recognition and activation of the immune cells, the paper presents phenotypic and functional characteristics of major and minor subpopulations of peripheral blood lymphocytes observed in 25 patients treated at the Surgery Department of the State Institution “Minsk Regional Clinical Hospital” (Republic of Belarus) from 2018 to 2020. The detected changes in peripheral blood lymphocyte phenotype of inflammatory bowel diseases patients suggest distinct immunological profiles prevailing in the damage mechanisms in Crohn’s disease and ulcerative colitis. I.e., in Crohn’s disease patients, B1 lymphocytes with CD19+CD5+ and NK cells in combination with increased CD56bright population, as well as NK T cells with anti-inflammatory and regulatory activity are involved into genesis of the disease. In ulcerative colitis, T, B, NK lymphocytes with pro-inflammatory phenotype and T lymphocytes with γδ T cell receptor may play a pathogenetic role in maintenance of chronic inflammation. With respect to functional significance of activating receptors, the number of TLR4- и CD89-positive cells may be used for developing immunological criteria/ biomarkers of therapeutic efficacy of new drugs. Studying interactions between innate and adaptive immunity will open new perspectives in understanding immunological disorders associated with chronic gastrointestinal inflammation.
{"title":"Phenotypic profile of peripheral blood lymphocytes in patients with inflammatory bowel diseases","authors":"M. Zafranskaya, H. Y. Adamovich, A. U. Varabei, A. M. Starastin, D. Nizheharodava","doi":"10.15789/1563-0625-ppo-2080","DOIUrl":"https://doi.org/10.15789/1563-0625-ppo-2080","url":null,"abstract":"Mechanisms of recognition and effector responses of immune system upon initiation and maintenance of immune-mediated inflammation and tissue damage in inflammatory bowel diseases, including Crohn’s disease and ulcerative colitis (UC), have been actively studied over recent time. Existing evidence suggests these diseases to be caused by abnormal immune response against intestinal flora microorganisms in genetically susceptible individuals. Despite available data on the features of immune disorders in ulcerative colitis and Crohn’s disease, there are still many questions about the involved minor lymphocyte subpopulations and contribution of various functionally active molecules, which play a key role in recognition and initiation of the immune response and can be considered biomarkers of a pathological process in inflammatory bowel diseases. The populations of T lymphocytes with γδT cell receptor, B1 cells and NK T lymphocytes are of greatest interest, as well as functionally active TLRs (Toll-like receptors), CD89, CD314, etc. Due to substantial progress in studying the nature of recognition and activation of the immune cells, the paper presents phenotypic and functional characteristics of major and minor subpopulations of peripheral blood lymphocytes observed in 25 patients treated at the Surgery Department of the State Institution “Minsk Regional Clinical Hospital” (Republic of Belarus) from 2018 to 2020. The detected changes in peripheral blood lymphocyte phenotype of inflammatory bowel diseases patients suggest distinct immunological profiles prevailing in the damage mechanisms in Crohn’s disease and ulcerative colitis. I.e., in Crohn’s disease patients, B1 lymphocytes with CD19+CD5+ and NK cells in combination with increased CD56bright population, as well as NK T cells with anti-inflammatory and regulatory activity are involved into genesis of the disease. In ulcerative colitis, T, B, NK lymphocytes with pro-inflammatory phenotype and T lymphocytes with γδ T cell receptor may play a pathogenetic role in maintenance of chronic inflammation. With respect to functional significance of activating receptors, the number of TLR4- и CD89-positive cells may be used for developing immunological criteria/ biomarkers of therapeutic efficacy of new drugs. Studying interactions between innate and adaptive immunity will open new perspectives in understanding immunological disorders associated with chronic gastrointestinal inflammation.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67111204","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 : 2021-01-10DOI: 10.15789/1563-0625-teo-000
S. Nedospasov
Tumor necrosis factor (TNF) is an important proinflammatory and immunoregulatory cytokine with several unique protective and homeostatic functions. Since TNF is a mediator of several pathologies and is a part of “cytokine storm”, its significance for clinical immunology is due to the fact that this cytokine is a target of commonly used anti-cytokine therapy in autoimmune and inflammatory diseases. In scientific literature and textbooks TNF is often goes as “TNFa”, implying the existence of at least TNFβ (indeed, such term was used for about 10 years in 80s and 90s to designate lymphotoxin). However, already 25 years ago such designation of lymphotoxin was cancelled “on scientific grounds”. Therefore, both in Russian and in English the term TNF should be used without “alpha”. Labels of the reagents related to TNFb that are offered by commercial companies are misleading.
{"title":"There exists only one tumor necrosis factor","authors":"S. Nedospasov","doi":"10.15789/1563-0625-teo-000","DOIUrl":"https://doi.org/10.15789/1563-0625-teo-000","url":null,"abstract":"Tumor necrosis factor (TNF) is an important proinflammatory and immunoregulatory cytokine with several unique protective and homeostatic functions. Since TNF is a mediator of several pathologies and is a part of “cytokine storm”, its significance for clinical immunology is due to the fact that this cytokine is a target of commonly used anti-cytokine therapy in autoimmune and inflammatory diseases. In scientific literature and textbooks TNF is often goes as “TNFa”, implying the existence of at least TNFβ (indeed, such term was used for about 10 years in 80s and 90s to designate lymphotoxin). However, already 25 years ago such designation of lymphotoxin was cancelled “on scientific grounds”. Therefore, both in Russian and in English the term TNF should be used without “alpha”. Labels of the reagents related to TNFb that are offered by commercial companies are misleading.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"94 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67112197","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 : 2021-01-10DOI: 10.15789/1563-0625-SLP-2062
D. V. Demina, A. O. Makeeva, L. M. Kudelya, E. V. Novikova, V. Kozlov
Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by quantitative (type I) or functional (type II) deficiency in C1 esterase inhibitor (C1-INH). It may be caused by new mutations in up to 20% of patients. Prevalence of HAE is uncertain but is estimated to be approximately 1 case per 50,000 persons, without known differences among ethnic groups. C1-INH protein is a serine protease inhibitor that is important in controlling vascular permeability by acting on the initial phase of the complement activation, blood clotting, and fibrinolysis. Deficiency in functional C1-INH protein permits release of bradykinin, a key mediator of vascular permeability. Symptoms typically begin since childhood, worsening at puberty, and persist throughout the life, with unpredictable clinical course. The patients with HAE suffer from recurrent, acute attacks of edema that can affect any body sites, causing potentially life-threatening disorders (laryngeal edema). Results of clinical studies show that minor traumas, stress and medical interventions may be frequent precipitants of swelling episodes, but many attacks occur without an apparent cause. Pregnancy-associated hormonal changes may affect the course of C1-INH angioedema attacks by worsening, improving, or having no impact at all, but a higher percentage of pregnant women experienced an increase in C1-INH-HAE attack rates. Therapeutic options for patients with HAE are limited during pregnancy. C1-INH concentrate is recommended as the first-line therapy for pregnant women with HAE for on-demand treatment, shortterm and long-term prophylaxis, due to its safety and efficiency. Other therapies, e.g., treatment with fresh frozen plasma, androgens, icatibant, antifibrinolytics, may show variable efficacy, or cause undesirable side effects. The case below illustrates the successful treatment of HAE in a pregnant woman with C1 esterase inhibitor (C1-INH) concentrate. This patient had a very mild course of HAE during her lifetime and didn’t get any treatment. During pregnancy, she experienced a significant increase in the frequency of attacks, and the decision was made to start replacement therapy with a plasma-derived, double virus-inactivated C1-INH concentrate as a long-term prophylaxis throughout the full term of her pregnancy, before, during and after the cesarean section delivery.
{"title":"Successful long-term prophylaxis of hereditary pregnancy-associated angioedema with plasma-derived C1-inhibitor concentrate: a case report","authors":"D. V. Demina, A. O. Makeeva, L. M. Kudelya, E. V. Novikova, V. Kozlov","doi":"10.15789/1563-0625-SLP-2062","DOIUrl":"https://doi.org/10.15789/1563-0625-SLP-2062","url":null,"abstract":"Hereditary angioedema (HAE) is a rare autosomal dominant disease caused by quantitative (type I) or functional (type II) deficiency in C1 esterase inhibitor (C1-INH). It may be caused by new mutations in up to 20% of patients. Prevalence of HAE is uncertain but is estimated to be approximately 1 case per 50,000 persons, without known differences among ethnic groups. C1-INH protein is a serine protease inhibitor that is important in controlling vascular permeability by acting on the initial phase of the complement activation, blood clotting, and fibrinolysis. Deficiency in functional C1-INH protein permits release of bradykinin, a key mediator of vascular permeability. Symptoms typically begin since childhood, worsening at puberty, and persist throughout the life, with unpredictable clinical course. The patients with HAE suffer from recurrent, acute attacks of edema that can affect any body sites, causing potentially life-threatening disorders (laryngeal edema). Results of clinical studies show that minor traumas, stress and medical interventions may be frequent precipitants of swelling episodes, but many attacks occur without an apparent cause. Pregnancy-associated hormonal changes may affect the course of C1-INH angioedema attacks by worsening, improving, or having no impact at all, but a higher percentage of pregnant women experienced an increase in C1-INH-HAE attack rates. Therapeutic options for patients with HAE are limited during pregnancy. C1-INH concentrate is recommended as the first-line therapy for pregnant women with HAE for on-demand treatment, shortterm and long-term prophylaxis, due to its safety and efficiency. Other therapies, e.g., treatment with fresh frozen plasma, androgens, icatibant, antifibrinolytics, may show variable efficacy, or cause undesirable side effects. The case below illustrates the successful treatment of HAE in a pregnant woman with C1 esterase inhibitor (C1-INH) concentrate. This patient had a very mild course of HAE during her lifetime and didn’t get any treatment. During pregnancy, she experienced a significant increase in the frequency of attacks, and the decision was made to start replacement therapy with a plasma-derived, double virus-inactivated C1-INH concentrate as a long-term prophylaxis throughout the full term of her pregnancy, before, during and after the cesarean section delivery.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"1215-1220"},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44512358","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 : 2021-01-10DOI: 10.15789/1563-0625-SEO-2082
A. V. Bateneva, S. Gamaley, Danilenko Ed, R. L. Lebedev
Influence of double-stranded RNA (dsRNA) from Saccharomyces cerevisiae yeast upon expression levels of the macrophage genes encoding TLR3 receptor, interferons alpha and beta (IFNα, IFNβ), 2’,5’-oligoadenylate synthetase (OAS) and protein kinase R (PKR) enzymes has been studied in the J774 mouse histiocytic cell culture and in vivo in Balb/c mice. It has been shown that dsRNA exerts a selective activating effect on genes of TLR3 receptor, antiviral proteins IFNα, IFNβ, and OAS, both in vitro and in vivo. With J774 cell culture, the highest induction capacity was observed for the IFNβ gene: 365 to 802-fold. The stimulatory effect was dependent on the dose of dsRNA in the range of 16.9 to 125 μg/ml. The preparation enhanced IFNα gene activity to lesser degree (more than 10-fold), TLR3 and OAS (3 to 4-fold), while the expression levels for these genes were not significantly dependent on the dose of dsRNA. The stimulating effect of dsRNA was dosedependent in murine peritoneal macrophages. The maximum activating effect of the preparation was shown upon administration of the effective antiviral dose (0.5 mg of dsRNA/kg). Five hours after intraperitoneal injection of dsRNA, the highest level of mRNA synthesis was observed for IFNα (54-fold), OAS (43-fold) and TLR3 (28-fold) genes. Expression of the IFNβ gene increased to a lesser degree (9-fold). An increase in the dose of preparation to 1.5 mg/kg led to decrease of the stimulatory effect. Expression levels of the IFNα, TLR3, and OAS genes in that case decreased by 2-4-fold as compared to a lower dose, and the PKR gene expression was 5-fold lower compared to the control. One day after dsRNA administration, a tendency was observed for both experimental groups towards a decreased transcription of macrophage genes, if compared with the 5-hour term. The weakening of gene activity was less pronounced in animals treated with dsRNA at the dose of 1.5 mg/kg. The transcription indices for IFNβ, OAS, and TLR3 genes were much higher during this period (5-10-fold higher than the control values). The dynamics of PKR gene transcription in both experimental systems was significantly different from the expression of other studied genes. The dsRNA preparation at this dose range did not have a pronounced stimulatory effect upon expression of this gene. A moderate increase in PKR gene activity in macrophages of mice was observed only a day following intraperitoneal administration of dsRNA. Concentrations and length of dsRNA molecules are known to be critical factors to the PKR gene activation. An ability to increase the expression of the gene is shown at low dsRNA concentrations (10-7 g/ml and below), while highly polymeric dsRNAs weaken the gene activity. Since the doses and concentrations of dsRNA used in our experiments were significantly different from those mentioned above, it could, in general, affect regulation of PKR gene transcription towards reduction of the stimulatory effect.
{"title":"Stimulating effect of double-stranded yeast RNA on the activity of interferon system genes","authors":"A. V. Bateneva, S. Gamaley, Danilenko Ed, R. L. Lebedev","doi":"10.15789/1563-0625-SEO-2082","DOIUrl":"https://doi.org/10.15789/1563-0625-SEO-2082","url":null,"abstract":"Influence of double-stranded RNA (dsRNA) from Saccharomyces cerevisiae yeast upon expression levels of the macrophage genes encoding TLR3 receptor, interferons alpha and beta (IFNα, IFNβ), 2’,5’-oligoadenylate synthetase (OAS) and protein kinase R (PKR) enzymes has been studied in the J774 mouse histiocytic cell culture and in vivo in Balb/c mice. It has been shown that dsRNA exerts a selective activating effect on genes of TLR3 receptor, antiviral proteins IFNα, IFNβ, and OAS, both in vitro and in vivo. With J774 cell culture, the highest induction capacity was observed for the IFNβ gene: 365 to 802-fold. The stimulatory effect was dependent on the dose of dsRNA in the range of 16.9 to 125 μg/ml. The preparation enhanced IFNα gene activity to lesser degree (more than 10-fold), TLR3 and OAS (3 to 4-fold), while the expression levels for these genes were not significantly dependent on the dose of dsRNA. The stimulating effect of dsRNA was dosedependent in murine peritoneal macrophages. The maximum activating effect of the preparation was shown upon administration of the effective antiviral dose (0.5 mg of dsRNA/kg). Five hours after intraperitoneal injection of dsRNA, the highest level of mRNA synthesis was observed for IFNα (54-fold), OAS (43-fold) and TLR3 (28-fold) genes. Expression of the IFNβ gene increased to a lesser degree (9-fold). An increase in the dose of preparation to 1.5 mg/kg led to decrease of the stimulatory effect. Expression levels of the IFNα, TLR3, and OAS genes in that case decreased by 2-4-fold as compared to a lower dose, and the PKR gene expression was 5-fold lower compared to the control. One day after dsRNA administration, a tendency was observed for both experimental groups towards a decreased transcription of macrophage genes, if compared with the 5-hour term. The weakening of gene activity was less pronounced in animals treated with dsRNA at the dose of 1.5 mg/kg. The transcription indices for IFNβ, OAS, and TLR3 genes were much higher during this period (5-10-fold higher than the control values). The dynamics of PKR gene transcription in both experimental systems was significantly different from the expression of other studied genes. The dsRNA preparation at this dose range did not have a pronounced stimulatory effect upon expression of this gene. A moderate increase in PKR gene activity in macrophages of mice was observed only a day following intraperitoneal administration of dsRNA. Concentrations and length of dsRNA molecules are known to be critical factors to the PKR gene activation. An ability to increase the expression of the gene is shown at low dsRNA concentrations (10-7 g/ml and below), while highly polymeric dsRNAs weaken the gene activity. Since the doses and concentrations of dsRNA used in our experiments were significantly different from those mentioned above, it could, in general, affect regulation of PKR gene transcription towards reduction of the stimulatory effect.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67111809","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 : 2021-01-10DOI: 10.15789/1563-0625-GSF-2066
M. Byazrova, A. Toptygina, T. Mitina, A. Filatov
B cell stimulation develops upon vaccination, thus causing occurrence of activated B cells (plasmoblasts) in bloodstream. Similar cells are also observed in some viral infections. The contents of plasmablasts may be a marker of successful vaccination, or a diagnostic feature of ongoing infection. The plasmablasts are normally represented by a small cell subpopulation which is not easy to detect. A study was performed with 15 healthy volunteers who were subjected to a single immunization with a recombinant vaccine against hepatitis B virus. To identify the plasmablasts, we have used labeled antibodies prepared in our laboratory. These reagents were previously validated for counting the plasmablasts. Different gating strategies for plasmablast gating have been compared. Upon staining of lymphocytes from immunized volunteers, we observed a distinct cluster of plasmablasts with CD27 ++ CD38 ++ phenotype using the following antibody set: CD19-PE, CD3/CD14/CD16-FITC, CD27-PC5.5 and CD38-PC7. Inclusion of a CD20-FITC antibody into the panel caused an increase of CD27 ++ CD38 ++ plasmablast ratio among CD19 + lymphocytes to > 60%. Upon substitution of CD38 antibody by anti-CD71, a distinct plasmablast cluster was again revealed, which contained ca. 5 per cent В cells. Two strategies for the plasmablast gating using the CD27/ CD38 and CD27/CD71 combinations were compared in dynamics with lymphocyte samples from a single vaccinated volunteer. When applying the CD27/CD38 combination, a sharp and pronounced plasmablast peak was registered on day 7 post-vaccination. With CD27/CD71 combination, the peak was extended between day 7 and day 14 following immunization. Hence, time kinetics of the CD27 + CD71 + population proved to be different from occurrence of classic plasmablasts with CD27 ++ CD38 ++ phenotype. This finding suggests that the CD27 ++ CD71 + population contains both plasmablasts and other types of activated B cells. A minor HBV surface antigen was prepared and labeled with phycoerythrin (HBsAg-PE), thus allowing to quantify the antigen-specific plasmablasts. The results of HBsAg-PE-based detection of antigen-specific cells were in compliance with the data obtained by ELISpot technique. At the present time, we use the original plasmablast gating technique for detection of activated B cells in SARS-CoV-2 infection. At the next step, this technique will be applied to sorting of antigen-specific B cells, thus permitting sequencing of Ig genes and design of novel human antibodies against viral antigens. B cell stimulation develops upon vaccination, thus causing occurrence of activated B cells (plasmoblasts) in bloodstream. Similar cells are also observed in some viral infections. The contents of plasmablasts may be a marker of successful vaccination, or a diagnostic feature of ongoing infection. The plasmablasts are normally represented by a small cell subpopulation which is not easy to detect. A study was performed with 15 healthy volunteers who were
{"title":"Gating strategy for plasmablast enumeration after hepatitis B vaccination","authors":"M. Byazrova, A. Toptygina, T. Mitina, A. Filatov","doi":"10.15789/1563-0625-GSF-2066","DOIUrl":"https://doi.org/10.15789/1563-0625-GSF-2066","url":null,"abstract":"B cell stimulation develops upon vaccination, thus causing occurrence of activated B cells (plasmoblasts) in bloodstream. Similar cells are also observed in some viral infections. The contents of plasmablasts may be a marker of successful vaccination, or a diagnostic feature of ongoing infection. The plasmablasts are normally represented by a small cell subpopulation which is not easy to detect. A study was performed with 15 healthy volunteers who were subjected to a single immunization with a recombinant vaccine against hepatitis B virus. To identify the plasmablasts, we have used labeled antibodies prepared in our laboratory. These reagents were previously validated for counting the plasmablasts. Different gating strategies for plasmablast gating have been compared. Upon staining of lymphocytes from immunized volunteers, we observed a distinct cluster of plasmablasts with CD27 ++ CD38 ++ phenotype using the following antibody set: CD19-PE, CD3/CD14/CD16-FITC, CD27-PC5.5 and CD38-PC7. Inclusion of a CD20-FITC antibody into the panel caused an increase of CD27 ++ CD38 ++ plasmablast ratio among CD19 + lymphocytes to > 60%. Upon substitution of CD38 antibody by anti-CD71, a distinct plasmablast cluster was again revealed, which contained ca. 5 per cent В cells. Two strategies for the plasmablast gating using the CD27/ CD38 and CD27/CD71 combinations were compared in dynamics with lymphocyte samples from a single vaccinated volunteer. When applying the CD27/CD38 combination, a sharp and pronounced plasmablast peak was registered on day 7 post-vaccination. With CD27/CD71 combination, the peak was extended between day 7 and day 14 following immunization. Hence, time kinetics of the CD27 + CD71 + population proved to be different from occurrence of classic plasmablasts with CD27 ++ CD38 ++ phenotype. This finding suggests that the CD27 ++ CD71 + population contains both plasmablasts and other types of activated B cells. A minor HBV surface antigen was prepared and labeled with phycoerythrin (HBsAg-PE), thus allowing to quantify the antigen-specific plasmablasts. The results of HBsAg-PE-based detection of antigen-specific cells were in compliance with the data obtained by ELISpot technique. At the present time, we use the original plasmablast gating technique for detection of activated B cells in SARS-CoV-2 infection. At the next step, this technique will be applied to sorting of antigen-specific B cells, thus permitting sequencing of Ig genes and design of novel human antibodies against viral antigens. B cell stimulation develops upon vaccination, thus causing occurrence of activated B cells (plasmoblasts) in bloodstream. Similar cells are also observed in some viral infections. The contents of plasmablasts may be a marker of successful vaccination, or a diagnostic feature of ongoing infection. The plasmablasts are normally represented by a small cell subpopulation which is not easy to detect. A study was performed with 15 healthy volunteers who were ","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"22 1","pages":"1185-1194"},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44336379","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 : 2021-01-10DOI: 10.15789/1563-0625-bpi-2090
N. Serebryanaya, P. Yakutseni
Participation of blood platelets in the development of sepsis is clearly illustrated by hemocoagulation disorders and frequently observed thrombocytopenia. In the patients with sepsis, thrombocytopenia develops rapidly, with minimal platelet counts registered on the fourth day of observation, after which the platelet counts usually rise. Continuous thrombocytopenia and absence of a relative increase in platelets are considered predictors of patient death. The mechanisms of thrombocytopenia developing in sepsis are quite diverse, but the processes in periphery are prevailing, e.g., the so-called “platelet consumption” which is determined by their activation, chemotaxis and isolation in the microvasculature. Recently, a mechanism has been identified for the accelerated removal of platelets with desialized surface glycoproteins from the circulation. Sialidases, also known as neuraminidases, are widely present in viruses and bacteria, and pharmacological inhibition of sialidases is able to withstand thrombocytopenia in the infectious process. The key role of platelets in the development of septic shock was revealed. Sequestration of platelets in the microvessels of the lungs and brain (manifesting as thrombocytopenia) is accompanied by rapid serotonin release, thus underlying the main clinical manifestations, e.g., decreased blood pressure, heart rate and increased capillary permeability. To counteract sharp release of this mediator, pharmacological attempts are made to inhibit the SERT transporter by means of selective serotonin reuptake inhibitors. Blood platelets are key participants in the pathogenesis of multiple organ failure syndromes, such as acute renal damage, acute respiratory distress syndrome, myocardial dysfunction, and sepsis-associated encephalopathy. To restore impaired vascular permeability in these conditions, in particular, sepsis-associated encephalopathy, a pharmacological S1P receptor mimetic is under study. The review specifies possible pathogenetically significant targets that can be used to perform pharmacological correction of conditions associated with sepsis and concomitant thrombocytopenia.
{"title":"Blood platelets in the development of sepsis, septic shock and multiple organ failure syndrome","authors":"N. Serebryanaya, P. Yakutseni","doi":"10.15789/1563-0625-bpi-2090","DOIUrl":"https://doi.org/10.15789/1563-0625-bpi-2090","url":null,"abstract":"Participation of blood platelets in the development of sepsis is clearly illustrated by hemocoagulation disorders and frequently observed thrombocytopenia. In the patients with sepsis, thrombocytopenia develops rapidly, with minimal platelet counts registered on the fourth day of observation, after which the platelet counts usually rise. Continuous thrombocytopenia and absence of a relative increase in platelets are considered predictors of patient death. The mechanisms of thrombocytopenia developing in sepsis are quite diverse, but the processes in periphery are prevailing, e.g., the so-called “platelet consumption” which is determined by their activation, chemotaxis and isolation in the microvasculature. Recently, a mechanism has been identified for the accelerated removal of platelets with desialized surface glycoproteins from the circulation. Sialidases, also known as neuraminidases, are widely present in viruses and bacteria, and pharmacological inhibition of sialidases is able to withstand thrombocytopenia in the infectious process. The key role of platelets in the development of septic shock was revealed. Sequestration of platelets in the microvessels of the lungs and brain (manifesting as thrombocytopenia) is accompanied by rapid serotonin release, thus underlying the main clinical manifestations, e.g., decreased blood pressure, heart rate and increased capillary permeability. To counteract sharp release of this mediator, pharmacological attempts are made to inhibit the SERT transporter by means of selective serotonin reuptake inhibitors. Blood platelets are key participants in the pathogenesis of multiple organ failure syndromes, such as acute renal damage, acute respiratory distress syndrome, myocardial dysfunction, and sepsis-associated encephalopathy. To restore impaired vascular permeability in these conditions, in particular, sepsis-associated encephalopathy, a pharmacological S1P receptor mimetic is under study. The review specifies possible pathogenetically significant targets that can be used to perform pharmacological correction of conditions associated with sepsis and concomitant thrombocytopenia.","PeriodicalId":85139,"journal":{"name":"Medical immunology (London, England)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67108023","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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