Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13957-cea
Natalya D. Abramova, E. A. Meremyanina, N. O. Kalyuzhnaya, A. V. Poddubikov, M. P. Kostinov, V. V. Grechenko, O. A. Svitich
Most respiratory viral infections proceed in mild form including COVID-19. Gowever, some patients experience severe systemic inflammation, tissue damage, acute respiratory distress syndrome, and cytokine storm with potentially lethal outcomes. The cytokines have been thought to play an important role in immunopathology of viral infection. However, an excessive immune response, manifesting as massive release of pro-inflammatory cytokines, may cause immune damage in the body. Production and release of the cytokines in healthy individuals presumes a significant balance of inflammatory and homeostatic factors. Meanwhile, in the case of COVID-19 disease, uncontrolled increased production of cytokines often occurs with fatal consequences for patients. The aim of this work was to study the level of IL-1, IL-18 and TNF gene expression, as well as production of these cytokines at the level of mucous membranes of the upper respiratory tract, in particular in oral cavity, in patients with severe COVID-19 disease.
The present study included patients who recovered from severe COVID-19. The control group consisted of conditionally healthy individuals. Expression levels of the IL-1, IL-18, and TNF genes were determined by RT-PCR. The levels of IL-1, IL-18 and TNF protein production were determined by multiplex enzyme immunoassay.
The expression levels of IL-1, IL-18 were reduced at the onset of the disease, as well as in the midpoint of the COVID-19 disease, but increased on the 30th day. The protein production of these cytokines was also reduced in the first days from the onset of the disease. The levels of pro-inflammatory TNF cytokine was high at the onset of the disease. The level of TNF production at the onset of the disease was also higher relative to the control group. Subsequently, the TNF gene expression levels decreased upon progression of the disease.
Thus, the increased expression level of pro-inflammatory cytokines may be explained by the fact that the S protein of the SARS-CoV-2 virus induces increased expression of these cytokines in human monocytes. Meanwhile, appropriate protein levels remain low, especially on day 1 from the onset of the disease. Thus, one may conclude that the virus triggers pyropotosis, however, within 15-30 days from the onset of the disease, when viral replication is already minimal.
{"title":"Сytokine expression and production in severe cases of SARS-CoV-2 infection","authors":"Natalya D. Abramova, E. A. Meremyanina, N. O. Kalyuzhnaya, A. V. Poddubikov, M. P. Kostinov, V. V. Grechenko, O. A. Svitich","doi":"10.46235/1028-7221-13957-cea","DOIUrl":"https://doi.org/10.46235/1028-7221-13957-cea","url":null,"abstract":"Most respiratory viral infections proceed in mild form including COVID-19. Gowever, some patients experience severe systemic inflammation, tissue damage, acute respiratory distress syndrome, and cytokine storm with potentially lethal outcomes. The cytokines have been thought to play an important role in immunopathology of viral infection. However, an excessive immune response, manifesting as massive release of pro-inflammatory cytokines, may cause immune damage in the body. Production and release of the cytokines in healthy individuals presumes a significant balance of inflammatory and homeostatic factors. Meanwhile, in the case of COVID-19 disease, uncontrolled increased production of cytokines often occurs with fatal consequences for patients. The aim of this work was to study the level of IL-1, IL-18 and TNF gene expression, as well as production of these cytokines at the level of mucous membranes of the upper respiratory tract, in particular in oral cavity, in patients with severe COVID-19 disease.
 The present study included patients who recovered from severe COVID-19. The control group consisted of conditionally healthy individuals. Expression levels of the IL-1, IL-18, and TNF genes were determined by RT-PCR. The levels of IL-1, IL-18 and TNF protein production were determined by multiplex enzyme immunoassay.
 The expression levels of IL-1, IL-18 were reduced at the onset of the disease, as well as in the midpoint of the COVID-19 disease, but increased on the 30th day. The protein production of these cytokines was also reduced in the first days from the onset of the disease. The levels of pro-inflammatory TNF cytokine was high at the onset of the disease. The level of TNF production at the onset of the disease was also higher relative to the control group. Subsequently, the TNF gene expression levels decreased upon progression of the disease.
 Thus, the increased expression level of pro-inflammatory cytokines may be explained by the fact that the S protein of the SARS-CoV-2 virus induces increased expression of these cytokines in human monocytes. Meanwhile, appropriate protein levels remain low, especially on day 1 from the onset of the disease. Thus, one may conclude that the virus triggers pyropotosis, however, within 15-30 days from the onset of the disease, when viral replication is already minimal.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"17 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13534-iol
V. S. Gogoleva, M. S. Drutskaya, Sergei A. Nedospasov
Complex immunobiology of lymphotoxin (LT) is due to multiple modalities of signal transduction, involving a soluble homotrimer and membrane-bound heterotrimers that engage at least three different receptors. While LT is crucial for the formation and maintenance of secondary lymphoid organs, its overproduction is observed in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Initially, LT was considered pathogenic in the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, as demonstrated by the resistance of mice with genetic LT inactivation to EAE induction. However, conflicting observations arose when EAE was induced in RAG1-deficient mice that underwent adoptive bone marrow transfer from LT-deficient mice, thereby calling into question previous conclusions about the role of LT in EAE development.
This study aimed to investigate the role of LT in MOG35-55-induced EAE using mice deficient in LT or its membrane receptor, LTR. LT knockout mice used here were designed to avoid the artifact involving TNF gene downregulation in myeloid cells, which occurred in the conventional LT knockout mice.
Surprisingly, LT-deficient mice with normal TNF expression developed EAE clinically comparable to wild-type mice. Conversely, genetic inactivation of LTR delayed EAE onset. However, during the later stages of the disease, LTR deletion exacerbated clinical symptoms of EAE.
These findings demonstrate that the involvement of LT in EAE development is more complex than previously estimated, and that LTR exhibits diverse functions depending on the disease stage: pathogenic at the early stage and protective at the later stages of EAE.
{"title":"Immunobiology of lymphotoxin: role in a mouse model of multiple sclerosis","authors":"V. S. Gogoleva, M. S. Drutskaya, Sergei A. Nedospasov","doi":"10.46235/1028-7221-13534-iol","DOIUrl":"https://doi.org/10.46235/1028-7221-13534-iol","url":null,"abstract":"Complex immunobiology of lymphotoxin (LT) is due to multiple modalities of signal transduction, involving a soluble homotrimer and membrane-bound heterotrimers that engage at least three different receptors. While LT is crucial for the formation and maintenance of secondary lymphoid organs, its overproduction is observed in autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. Initially, LT was considered pathogenic in the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, as demonstrated by the resistance of mice with genetic LT inactivation to EAE induction. However, conflicting observations arose when EAE was induced in RAG1-deficient mice that underwent adoptive bone marrow transfer from LT-deficient mice, thereby calling into question previous conclusions about the role of LT in EAE development.
 This study aimed to investigate the role of LT in MOG35-55-induced EAE using mice deficient in LT or its membrane receptor, LTR. LT knockout mice used here were designed to avoid the artifact involving TNF gene downregulation in myeloid cells, which occurred in the conventional LT knockout mice.
 Surprisingly, LT-deficient mice with normal TNF expression developed EAE clinically comparable to wild-type mice. Conversely, genetic inactivation of LTR delayed EAE onset. However, during the later stages of the disease, LTR deletion exacerbated clinical symptoms of EAE.
 These findings demonstrate that the involvement of LT in EAE development is more complex than previously estimated, and that LTR exhibits diverse functions depending on the disease stage: pathogenic at the early stage and protective at the later stages of EAE.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"56 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13987-ivp
Valeria P. Timganova, K. Y. Shardina, M. S. Bochkova, D. I. Usanina, S. A. Zamorina
Myeloid-derived suppressor cells (MDSCs) are of interest as key regulators of the immune response for the development and improvement of cellular technologies in biomedicine. Enhancing the suppressive activity of these cells is important for developing therapies for autoimmune diseases and miscarriages, and their suppression may be useful in the treatment of cancer, since MDSCs are known to suppress antitumor immunity. However, there is a problem that prevents the active study of MDSCs, i.e., the difficulty in obtaining sufficient numbers of this cell population. Isolation of MDSCs in cancer patients poses an ethical challenge. Moreover, these MDSC may differ in subpopulation composition and suppressive activity due to individual factors. Researchers who generate human MDSC from bone marrow cells may also face similar problems. Therefore, finding a reliable and affordable source of these cells to facilitate the study of their functions is extremely important. Attempts to obtain human MDSCs in vitro have been ongoing for a long time. GM- CSF, IL-6, IL- 1, IL-4, PGE2, LPS, M-CSF, IFN are described as factors that induce the ex vivo MDSC differentiation. However, despite multiple factors used, not all protocols are clearly reproducible, leading to generation of a sufficient number of cells in the target population. Previously, we had also developed a scheme for MDSC differentiation from CD11b+ cells derived from human peripheral blood, which made it possible to obtain a tangible but still insufficient percentage of cells to study functional activity.
To increase the number of MDSCs in cultures, we developed a protocol aimed for differentiation of these cells from peripheral blood monocytes (CD14+ cells) previously transformed into PCMO (programmed cells of monocytic origin). The monocytes isolated by immunomagnetic separation were cultured in a de-differentiating medium (complete culture medium supplemented with M-CSF, IL-3 and -mercaptoethanol) for one week. Later on, the medium was replaced by the addition of GM-CSF, being cultured for three days, followed by addition of LPS and IL-1 in order to induce suppressive activity. We have found that culturing CD14+ cells on a two-week schedule with prior creation of dedifferentiation conditions resulted in a slightly decreased percentage of viable cells in culture. However, there was a trend towards an increased ratio of MDSCs in culture (from an average of 34 to 40%) and an increase in their suppressive activity (arginase and IDO expression). The percentage of Arg+ cells increased by average of 10%, and IDO+ cells, by 16%. Moreover, the percentage of mature M-MDSCs was significantly (several-fold) higher when compared with differentiation protocol using CD11b+ cells. Hence, this method of MDSCs production enables us to increase the number of cells belonging to the conditionally mature monocyte subpopulation of MDSCs, as well as the percentage of functional suppressor cells in the population. The d
{"title":"<i>In vitro</i> production of myeloid-derived suppressor cells from peripheral blood monocytes","authors":"Valeria P. Timganova, K. Y. Shardina, M. S. Bochkova, D. I. Usanina, S. A. Zamorina","doi":"10.46235/1028-7221-13987-ivp","DOIUrl":"https://doi.org/10.46235/1028-7221-13987-ivp","url":null,"abstract":"Myeloid-derived suppressor cells (MDSCs) are of interest as key regulators of the immune response for the development and improvement of cellular technologies in biomedicine. Enhancing the suppressive activity of these cells is important for developing therapies for autoimmune diseases and miscarriages, and their suppression may be useful in the treatment of cancer, since MDSCs are known to suppress antitumor immunity. However, there is a problem that prevents the active study of MDSCs, i.e., the difficulty in obtaining sufficient numbers of this cell population. Isolation of MDSCs in cancer patients poses an ethical challenge. Moreover, these MDSC may differ in subpopulation composition and suppressive activity due to individual factors. Researchers who generate human MDSC from bone marrow cells may also face similar problems. Therefore, finding a reliable and affordable source of these cells to facilitate the study of their functions is extremely important. Attempts to obtain human MDSCs in vitro have been ongoing for a long time. GM- CSF, IL-6, IL- 1, IL-4, PGE2, LPS, M-CSF, IFN are described as factors that induce the ex vivo MDSC differentiation. However, despite multiple factors used, not all protocols are clearly reproducible, leading to generation of a sufficient number of cells in the target population. Previously, we had also developed a scheme for MDSC differentiation from CD11b+ cells derived from human peripheral blood, which made it possible to obtain a tangible but still insufficient percentage of cells to study functional activity.
 To increase the number of MDSCs in cultures, we developed a protocol aimed for differentiation of these cells from peripheral blood monocytes (CD14+ cells) previously transformed into PCMO (programmed cells of monocytic origin). The monocytes isolated by immunomagnetic separation were cultured in a de-differentiating medium (complete culture medium supplemented with M-CSF, IL-3 and -mercaptoethanol) for one week. Later on, the medium was replaced by the addition of GM-CSF, being cultured for three days, followed by addition of LPS and IL-1 in order to induce suppressive activity. We have found that culturing CD14+ cells on a two-week schedule with prior creation of dedifferentiation conditions resulted in a slightly decreased percentage of viable cells in culture. However, there was a trend towards an increased ratio of MDSCs in culture (from an average of 34 to 40%) and an increase in their suppressive activity (arginase and IDO expression). The percentage of Arg+ cells increased by average of 10%, and IDO+ cells, by 16%. Moreover, the percentage of mature M-MDSCs was significantly (several-fold) higher when compared with differentiation protocol using CD11b+ cells. Hence, this method of MDSCs production enables us to increase the number of cells belonging to the conditionally mature monocyte subpopulation of MDSCs, as well as the percentage of functional suppressor cells in the population. The d","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"88 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136061428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13925-cco
Elena D. Gavrilova, E. V. Goiman, E. N. Demchenko, D. V. Demina, N. N. Volskiy, V. A. Kozlov
Many studies have shown that the level of cell-free DNA (cfDNA) in blood of patients with oncological diseases, sepsis, systemic lupus erythematosus, and some rheumatic diseases significantly exceeds the value of similar index in healthy donors and is closely related to the clinical features of the disease. Systemic inflammatory response is among the most frequent pathophysiological processes along with markedly changed levels of cfDNA in blood plasma. The levels of cfDNA in blood plasma of patients with RA are shown to be closely associated with a shifted balance of helpers to the Th1-side. It is an adequate intensity index of inflammatory processes and effectiveness of therapy. At the same time, there only limited number of works concerning changes in cfDNA levels in pathological processes with predominance of Th2 lymphocytes. According to generally accepted concept, the pathogenesis of bronchial asthma is of distinct interest, being critically dependent on the production of specific antibodies controlled by activated Th2 lymphocytes. The aim of this work was to study the level of cfDNA in blood and compare its changes with intensity of NETs and inflammation in patients with asthma. The study included 20 patients with asthma, who underwent hospital treatment at the Department Allergology (Clinic of Immunopathology, RIFCI, Novosibirsk), and 10 conditionally healthy donors. We have shown that, upon admission to the clinic, the level of cfDNA in patients with asthma was significantly reduced against the control group of healthy donors. After a course of therapy, the average level of cfDNA in patients plasma was increased and did not differ statistically significantly from this index in controls. The data obtained for other parameters indicate that the patients with asthma did not reveal any signs of pronounced systemic inflammatory response. One should suggest that the observed changes in the level of cfDNA in blood plasma in bronchial asthma are not caused by chronic inflammatory process in lungs of these patients, but they are determined by some other pathophysiological mechanisms. It has been shown that the level of in vitro stimulated NETs in patients with asthma is higher than in healthy donors, thus being consistent with current opinions on the role of neutrophils in pathogenesis of asthma.
{"title":"Characteristic changes of extracellular Dna levels, indices of netosis and inflammation in peripheral blood in patients with asthma","authors":"Elena D. Gavrilova, E. V. Goiman, E. N. Demchenko, D. V. Demina, N. N. Volskiy, V. A. Kozlov","doi":"10.46235/1028-7221-13925-cco","DOIUrl":"https://doi.org/10.46235/1028-7221-13925-cco","url":null,"abstract":"Many studies have shown that the level of cell-free DNA (cfDNA) in blood of patients with oncological diseases, sepsis, systemic lupus erythematosus, and some rheumatic diseases significantly exceeds the value of similar index in healthy donors and is closely related to the clinical features of the disease. Systemic inflammatory response is among the most frequent pathophysiological processes along with markedly changed levels of cfDNA in blood plasma. The levels of cfDNA in blood plasma of patients with RA are shown to be closely associated with a shifted balance of helpers to the Th1-side. It is an adequate intensity index of inflammatory processes and effectiveness of therapy. At the same time, there only limited number of works concerning changes in cfDNA levels in pathological processes with predominance of Th2 lymphocytes. According to generally accepted concept, the pathogenesis of bronchial asthma is of distinct interest, being critically dependent on the production of specific antibodies controlled by activated Th2 lymphocytes. The aim of this work was to study the level of cfDNA in blood and compare its changes with intensity of NETs and inflammation in patients with asthma. The study included 20 patients with asthma, who underwent hospital treatment at the Department Allergology (Clinic of Immunopathology, RIFCI, Novosibirsk), and 10 conditionally healthy donors. We have shown that, upon admission to the clinic, the level of cfDNA in patients with asthma was significantly reduced against the control group of healthy donors. After a course of therapy, the average level of cfDNA in patients plasma was increased and did not differ statistically significantly from this index in controls. The data obtained for other parameters indicate that the patients with asthma did not reveal any signs of pronounced systemic inflammatory response. One should suggest that the observed changes in the level of cfDNA in blood plasma in bronchial asthma are not caused by chronic inflammatory process in lungs of these patients, but they are determined by some other pathophysiological mechanisms. It has been shown that the level of in vitro stimulated NETs in patients with asthma is higher than in healthy donors, thus being consistent with current opinions on the role of neutrophils in pathogenesis of asthma.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13908-peo
M. G. Atazhakhova, Irina V. Nesterova, G. A. Chudilova, V. A. Matushkina, S. V. Kovaleva, V. N. Chapurina
Post-COVID syndrome (PCS) is a multisystem inflammatory condition with manifestations of chronic fatigue syndrome (CFS) and cognitive disorders (CD), along with reactivation of chronic herpesvirus infections (HVI). The PCS manifestations require studying the molecular mechanisms associated with the production of IFN and receptor functions of neutrophil granulocytes (NG), which is relevant and promotes the search for immunotherapeutic strategies in patients with PCS. Our objective was to study the in vitro effects of recombinant interferon 2b (recIFN2b) on the phenotype of CD16+IFN/R1-CD119+, CD16+IFN/ R1+CD119+ subsets and functional activity of NG in patients with post-COVID syndrome and herpesvirus infections. Materials and methods: 45 patients (24-60 years old) with PCS and HVI (HSV 1, EBV, HHV6, CMV) comprised the study group 1 (SG1). A questionnaire was conducted to assess the severity of PCS symptoms using a point scale. We performed a study of the content and phenotype of NG subsets, i.e., the CD16+IFN/R1-CD119+, CD16+IFN/R1+CD119-, CD16+IFN/R1+CD119+ subpopulation, phagocytic and NADPH oxidase function of NG before and after in vitro incubation with recIFN2b (50 IU/ L, for 60 min, at 37 C) in the study group 1a (SG1a). The comparison group (CG) of 30 volunteers examined during the pre-COVID period. Results: We revealed more pronounced clinical manifestations of CFS and CD in SG1 patients with mixed HVI, than in mono-HVI cases. Increased expression density of all receptors was registered on CD16+IFN/R1+CD119-NG and CD16+IFN/R1-CD119+ NG, thus suggesting the NG activation with initiation of cytotoxicity or NETosis, a decrease in phagocytic function and intensity of NADPH oxidase activity with depletion of NG reserve capacity in SG1. We have obtained some data on the positive effect of recIFN2b in vitro (SG1a), e.g., decreased CD16 expression density and enhancement of IFN/R1 receptor expression in the CD16+IFN/R1+CD119- subset. In the CD16+IFN/R1-CD119+ subset, we have found persistence of increased MFI CD16 and MFI CD119 receptors, restoration of defective NG phagocytic function and reduced excessive activity of NADPH oxidases. Conclusion: The positive effects of the recIFN2b influence on deficient function of NG in PCS patients suggest an oppoptunity of using immunotherapy with a recIFN2b-based drug, combined with highly active antioxidants for treatment of various PCS manifestations including CFS, CD, HVI, thus, probably, ensuring adequate functioning of antiviral and regulatory mechanisms of the immune system.
{"title":"Positive effects of recombinant interferon α2b on the phenotype of CD16<sup>+</sup>INFα/βR1<sup>-</sup>CD119<sup>+</sup>, CD16<sup>+</sup>INFα/βR1<sup>+</sup>CD119<sup>-</sup> neutrophil granulocyte subset in patients with post-COVID syndrome and herpesvirus infections","authors":"M. G. Atazhakhova, Irina V. Nesterova, G. A. Chudilova, V. A. Matushkina, S. V. Kovaleva, V. N. Chapurina","doi":"10.46235/1028-7221-13908-peo","DOIUrl":"https://doi.org/10.46235/1028-7221-13908-peo","url":null,"abstract":"Post-COVID syndrome (PCS) is a multisystem inflammatory condition with manifestations of chronic fatigue syndrome (CFS) and cognitive disorders (CD), along with reactivation of chronic herpesvirus infections (HVI). The PCS manifestations require studying the molecular mechanisms associated with the production of IFN and receptor functions of neutrophil granulocytes (NG), which is relevant and promotes the search for immunotherapeutic strategies in patients with PCS. Our objective was to study the in vitro effects of recombinant interferon 2b (recIFN2b) on the phenotype of CD16+IFN/R1-CD119+, CD16+IFN/ R1+CD119+ subsets and functional activity of NG in patients with post-COVID syndrome and herpesvirus infections. Materials and methods: 45 patients (24-60 years old) with PCS and HVI (HSV 1, EBV, HHV6, CMV) comprised the study group 1 (SG1). A questionnaire was conducted to assess the severity of PCS symptoms using a point scale. We performed a study of the content and phenotype of NG subsets, i.e., the CD16+IFN/R1-CD119+, CD16+IFN/R1+CD119-, CD16+IFN/R1+CD119+ subpopulation, phagocytic and NADPH oxidase function of NG before and after in vitro incubation with recIFN2b (50 IU/ L, for 60 min, at 37 C) in the study group 1a (SG1a). The comparison group (CG) of 30 volunteers examined during the pre-COVID period. Results: We revealed more pronounced clinical manifestations of CFS and CD in SG1 patients with mixed HVI, than in mono-HVI cases. Increased expression density of all receptors was registered on CD16+IFN/R1+CD119-NG and CD16+IFN/R1-CD119+ NG, thus suggesting the NG activation with initiation of cytotoxicity or NETosis, a decrease in phagocytic function and intensity of NADPH oxidase activity with depletion of NG reserve capacity in SG1. We have obtained some data on the positive effect of recIFN2b in vitro (SG1a), e.g., decreased CD16 expression density and enhancement of IFN/R1 receptor expression in the CD16+IFN/R1+CD119- subset. In the CD16+IFN/R1-CD119+ subset, we have found persistence of increased MFI CD16 and MFI CD119 receptors, restoration of defective NG phagocytic function and reduced excessive activity of NADPH oxidases. Conclusion: The positive effects of the recIFN2b influence on deficient function of NG in PCS patients suggest an oppoptunity of using immunotherapy with a recIFN2b-based drug, combined with highly active antioxidants for treatment of various PCS manifestations including CFS, CD, HVI, thus, probably, ensuring adequate functioning of antiviral and regulatory mechanisms of the immune system.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"18 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13959-can
Olga V. Valikova, V. V. Zdor, V. A. Sarychev, Ya. N. Tikhonov, Andrey V. Boroda
Cytokines regulate the activity of hypothalamus pituitary adrenal hormonal axis, also affecting thyroid gland and ovaries. However, their exact role in pathogenesis of endocrine diseases is still under study. Altered cytokine secretion in autoimmune thyroid diseases and polycystic ovary syndrome is well known. Meanwhile, the main immunological predictors of severe prognosis in endocrinopathies and biomarkers for administration of targeted immunotherapy have not yet been determined. Therefore, our objective was to study the relationships between the cytokines and hormones in pathogenesis of autoimmune and non-autoimmune endocrinopathies, i.e., autoimmune thyroiditis (AIT), Graves disease (GD), nodular and multinodular goiter, polycystic ovary syndrome (PCOS).
101 patients with GD and 105 patients with AIT, 110 patients with PCOS were examined; 51 patients with nodular and multinodular euthyroid goiter and 50 healthy individuals; their average age was 34.52.9 years old. The study was approved by the Interdisciplinary Ethics Committee of the Pacific State Medical University. Clinical examination included ultrasonography. ELISA technique was applied for determination of thyroid and sex hormones, TSH, autoantibodies to TPO, TSH receptor, cytokines in blood serum, in follicular fluid samples, cell culture media (primary cultures of cumulus cells). Genetic studies were carried out with PCR. Morphological verification was performed by inverted microscopy CKX41 (Olympus) with a phase contrast system, camera AxioCam5 (Carl Zeiss) with software Zen 2, Blue Edition.
IL-6 and TNF in the blood serum of patients with PCOS were most significantly increased, Sharply decreased IFN/IL-10 ratio in blood serum and cumulus cell culture was found in PCOS when compared with controls. Significant changes in the content of thyroid hormones in GD and TSH in AIT have been proven to affect the hyperproduction of pro- and anti-inflammatory cytokines. Before treatrment, the direct or reverse corelations were found between the levels of cytokines and thyroid hormones in GD, and TSH in AIT. Subsequently, upon correction of hormonal disorders, these associations became weaker, or faded away. In patients with nodular and multinodular euthyroid goiter, only the IFN level was significantly increased, being twice as high as in the control group.
A significant imbalance in the ratio of Th1/Th2 marker cytokines and their hyperproduction in autoimmune thyroid diseases made it possible to characterize the cellular response system in autoimmune thyroid disorders as highly active and directly associated with thyroid dysfunction, performing its effector function under the impaired immunoregulation. The revealed changes in pro-inflammatory cytokines in polycystic ovary syndrome represent new immunological markers of fertility, which may be a promising target for pathogenetic immunotherapy.
{"title":"Сytokines as non-hormonal regulators in the pathogenesis of endocrinopathies","authors":"Olga V. Valikova, V. V. Zdor, V. A. Sarychev, Ya. N. Tikhonov, Andrey V. Boroda","doi":"10.46235/1028-7221-13959-can","DOIUrl":"https://doi.org/10.46235/1028-7221-13959-can","url":null,"abstract":"Cytokines regulate the activity of hypothalamus pituitary adrenal hormonal axis, also affecting thyroid gland and ovaries. However, their exact role in pathogenesis of endocrine diseases is still under study. Altered cytokine secretion in autoimmune thyroid diseases and polycystic ovary syndrome is well known. Meanwhile, the main immunological predictors of severe prognosis in endocrinopathies and biomarkers for administration of targeted immunotherapy have not yet been determined. Therefore, our objective was to study the relationships between the cytokines and hormones in pathogenesis of autoimmune and non-autoimmune endocrinopathies, i.e., autoimmune thyroiditis (AIT), Graves disease (GD), nodular and multinodular goiter, polycystic ovary syndrome (PCOS).
 101 patients with GD and 105 patients with AIT, 110 patients with PCOS were examined; 51 patients with nodular and multinodular euthyroid goiter and 50 healthy individuals; their average age was 34.52.9 years old. The study was approved by the Interdisciplinary Ethics Committee of the Pacific State Medical University. Clinical examination included ultrasonography. ELISA technique was applied for determination of thyroid and sex hormones, TSH, autoantibodies to TPO, TSH receptor, cytokines in blood serum, in follicular fluid samples, cell culture media (primary cultures of cumulus cells). Genetic studies were carried out with PCR. Morphological verification was performed by inverted microscopy CKX41 (Olympus) with a phase contrast system, camera AxioCam5 (Carl Zeiss) with software Zen 2, Blue Edition.
 IL-6 and TNF in the blood serum of patients with PCOS were most significantly increased, Sharply decreased IFN/IL-10 ratio in blood serum and cumulus cell culture was found in PCOS when compared with controls. Significant changes in the content of thyroid hormones in GD and TSH in AIT have been proven to affect the hyperproduction of pro- and anti-inflammatory cytokines. Before treatrment, the direct or reverse corelations were found between the levels of cytokines and thyroid hormones in GD, and TSH in AIT. Subsequently, upon correction of hormonal disorders, these associations became weaker, or faded away. In patients with nodular and multinodular euthyroid goiter, only the IFN level was significantly increased, being twice as high as in the control group.
 A significant imbalance in the ratio of Th1/Th2 marker cytokines and their hyperproduction in autoimmune thyroid diseases made it possible to characterize the cellular response system in autoimmune thyroid disorders as highly active and directly associated with thyroid dysfunction, performing its effector function under the impaired immunoregulation. The revealed changes in pro-inflammatory cytokines in polycystic ovary syndrome represent new immunological markers of fertility, which may be a promising target for pathogenetic immunotherapy.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"27 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13616-moe
Nikolay Y. Vasiliev, Ya. I. Kozlova, E. V. Frolova, A. E. Uchevatkina, L. V. Filippova, O. V. Aak, A. V. Sobolev, N. V. Vasilieva
Immunological characteristics of airway inflammation in asthma patients with sensitization to various fungal allergens are not well understood, and the search for new markers is necessary to establish future targets for targeted therapy. The purpose of our study was to assess the levels of eosinophilic inflammation markers of the respiratory tract in patients with severe asthma and allergic bronchopulmonary aspergillosis, depending on the spectrum of fungal sensitization.
The study included 31 patients with severe asthma with fungal sensitization and 29 patients with allergic bronchopulmonary aspergillosis (ABPA). The levels of total, specific IgE to fungal allergens and periostin in blood serum were determined by enzyme immunoassay. The study of basophil activation was performed by flow cytometry.
The patients with severe asthma and sensitization to Aspergillus spp. and Alternaria spp. had significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp. in the basophil activation test when compared with the group of asthma patients with sensitization to Aspergillus spp. only. In patients with ABPA with combined sensitization, we have found significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp.
The finding of pronounced eosinophilic type of inflammation in patients with asthma and combined sensitization to thermotolerant and thermolabile fungi may result from aggressive effect of fungal allergens on the barrier functions of bronchial epithelium, which should be taken into account when choosing therapeutic strategy and administration of immunobiological therapy.
{"title":"Markers of eosinophilic inflammation of airways in patients with fungal sensitilization","authors":"Nikolay Y. Vasiliev, Ya. I. Kozlova, E. V. Frolova, A. E. Uchevatkina, L. V. Filippova, O. V. Aak, A. V. Sobolev, N. V. Vasilieva","doi":"10.46235/1028-7221-13616-moe","DOIUrl":"https://doi.org/10.46235/1028-7221-13616-moe","url":null,"abstract":"Immunological characteristics of airway inflammation in asthma patients with sensitization to various fungal allergens are not well understood, and the search for new markers is necessary to establish future targets for targeted therapy. The purpose of our study was to assess the levels of eosinophilic inflammation markers of the respiratory tract in patients with severe asthma and allergic bronchopulmonary aspergillosis, depending on the spectrum of fungal sensitization.
 The study included 31 patients with severe asthma with fungal sensitization and 29 patients with allergic bronchopulmonary aspergillosis (ABPA). The levels of total, specific IgE to fungal allergens and periostin in blood serum were determined by enzyme immunoassay. The study of basophil activation was performed by flow cytometry.
 The patients with severe asthma and sensitization to Aspergillus spp. and Alternaria spp. had significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp. in the basophil activation test when compared with the group of asthma patients with sensitization to Aspergillus spp. only. In patients with ABPA with combined sensitization, we have found significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp.
 The finding of pronounced eosinophilic type of inflammation in patients with asthma and combined sensitization to thermotolerant and thermolabile fungi may result from aggressive effect of fungal allergens on the barrier functions of bronchial epithelium, which should be taken into account when choosing therapeutic strategy and administration of immunobiological therapy.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"199 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13931-cai
Svetlana V. Kovaleva, I. V. Nesterova, G. A. Chudilova, S. N. Pikturno, L. V. Lomtatidze
Failure of anti-infectious immune protection is considered a reason for the prolonged course and recurrence of chronic infectious and inflammatory diseases of pelvic organs (PID). Our aim was to evaluate the effect of an original hexapeptide (HP) on negatively altered subpopulations of neutrophil granulocytes (NG) CD11b+CD64-CD32+CD16+ and CD11b+CD64+CD32+CD16+, their phenotype and associated effector functions in immunocompromised women with PID.
35 women (20-40 years old) with PID were studied during the period of clinical exacerbation (study group 1, SG1). Study group 1a (SG1a) consisted of patients who underwent treatment including the HP injections (45 mcg/ mL, 1 ml intramuscularly once a day for 10 days). The comparison group (CG) consisted of 20 conditionally healthy women. The numbers of CD11b+CD64-CD32+CD16+NG and CD11b+CD64+CD32+CD16+NG cell subsets and the density of receptor expression, phagocytic and microbicidal function of NG were determined.
In SG1, decreased counts of the major NG subpopulation (CD11b+CD64-CD32+CD16+NG) was revealed (p 0.05), with a trend for increase of minor subset CD11b+CD64+CD32+CD16+NG (p 0.05). In the CD11b+CD64-CD32+CD16+NG subset, we noted a decreased expression of CD16 (1.4-fold), CD11b (2-fold) (p1, 2 0.05). In the minor subset CD11b+CD64+CD32+CD16+NG, the expression densities were decreased in CD16 (1.7-fold), CD11b (2.1-fold, p1, 2 0.05). At the same time, the phagocytic and microbicidal functions of NG were found to be decreased. In the course of immunomodulatory therapy with the HP-based drug, positive changes in immunological parameters were revealed. In SG1a, an increased number of major NC subset was observed, with an increase in the expression density of CD16 by 1.2 times, CD11b by 1.7 times relative to SG1 (p1, 2 0.05). The contents of minor NG subset tended to decrease, along with CD16 expression density reaching the indices of comparison group. CD11b increased 1.3 times relative to SG1 (p 0.05). Higher ratios of actively phagocytizing NG and their killing ability have been registered. Clinically, we observed faster regression of clinical PID exacerbation symptoms and decreased frequency of relapses 6 months after treatment in 88.6% of cases. The positive immunomodulatory effects of the HP-based drug upon altered subsets of CD11b+CD64-CD32+CD16+ and CD11b+CD64+CD32+CD16+ NGs, their phenotype and associated effector functions suggest an opportunity of its usage for the correction of NG dysfunctions in immunocompromised women with PID, thus providing stable clinical and immunological remission and protective effect.
{"title":"Clinical and immunological efficacy of immunomodulating hexapeptide associated with the restoration of CD11b<sup>+</sup>CD64<sup>-</sup>CD32<sup>+</sup>CD16<sup>+</sup> and CD11b<sup>+</sup>CD64<sup>+</sup>CD32<sup>+</sup>CD16<sup>+</sup> neutrophil granulocytes subset in women with chronic infectious and inflammatory diseases of the pelvic organs","authors":"Svetlana V. Kovaleva, I. V. Nesterova, G. A. Chudilova, S. N. Pikturno, L. V. Lomtatidze","doi":"10.46235/1028-7221-13931-cai","DOIUrl":"https://doi.org/10.46235/1028-7221-13931-cai","url":null,"abstract":"Failure of anti-infectious immune protection is considered a reason for the prolonged course and recurrence of chronic infectious and inflammatory diseases of pelvic organs (PID). Our aim was to evaluate the effect of an original hexapeptide (HP) on negatively altered subpopulations of neutrophil granulocytes (NG) CD11b+CD64-CD32+CD16+ and CD11b+CD64+CD32+CD16+, their phenotype and associated effector functions in immunocompromised women with PID.
 35 women (20-40 years old) with PID were studied during the period of clinical exacerbation (study group 1, SG1). Study group 1a (SG1a) consisted of patients who underwent treatment including the HP injections (45 mcg/ mL, 1 ml intramuscularly once a day for 10 days). The comparison group (CG) consisted of 20 conditionally healthy women. The numbers of CD11b+CD64-CD32+CD16+NG and CD11b+CD64+CD32+CD16+NG cell subsets and the density of receptor expression, phagocytic and microbicidal function of NG were determined.
 In SG1, decreased counts of the major NG subpopulation (CD11b+CD64-CD32+CD16+NG) was revealed (p 0.05), with a trend for increase of minor subset CD11b+CD64+CD32+CD16+NG (p 0.05). In the CD11b+CD64-CD32+CD16+NG subset, we noted a decreased expression of CD16 (1.4-fold), CD11b (2-fold) (p1, 2 0.05). In the minor subset CD11b+CD64+CD32+CD16+NG, the expression densities were decreased in CD16 (1.7-fold), CD11b (2.1-fold, p1, 2 0.05). At the same time, the phagocytic and microbicidal functions of NG were found to be decreased. In the course of immunomodulatory therapy with the HP-based drug, positive changes in immunological parameters were revealed. In SG1a, an increased number of major NC subset was observed, with an increase in the expression density of CD16 by 1.2 times, CD11b by 1.7 times relative to SG1 (p1, 2 0.05). The contents of minor NG subset tended to decrease, along with CD16 expression density reaching the indices of comparison group. CD11b increased 1.3 times relative to SG1 (p 0.05). Higher ratios of actively phagocytizing NG and their killing ability have been registered. Clinically, we observed faster regression of clinical PID exacerbation symptoms and decreased frequency of relapses 6 months after treatment in 88.6% of cases. The positive immunomodulatory effects of the HP-based drug upon altered subsets of CD11b+CD64-CD32+CD16+ and CD11b+CD64+CD32+CD16+ NGs, their phenotype and associated effector functions suggest an opportunity of its usage for the correction of NG dysfunctions in immunocompromised women with PID, thus providing stable clinical and immunological remission and protective effect.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"28 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-22DOI: 10.46235/1028-7221-13541-sii
M. P. Kostinov, N. D. Abramova, V. N. Osiptsov, V. R. Tatevosov, V. V. Gainitdinova, N. O. Kryukova, I. A. Baranova, E. A. Khromova, Elena S. Korovkina, A. G. Chuchalin, O. A. Svitich, K. V. Mashilov
The mucosal immunity performs an important function in prevention of respiratory infections including COVID-19. The search for approaches to activate the synthesis of post-infectious antibodies by correcting the factors of innate and adaptive immunity at mucous membranes of respiratory tract in patients with infection caused by the new coronavirus may be relevant for the treatment of patients with COVID-19. The aim of our study was to assess the concentrations of sIgA in the upper respiratory tract in patients with a confirmed diagnosis of Coronavirus infection caused by the COVID-19, and to evaluate the effect of an immunostimulating drug of bacterial origin upon the sIgA secretion.
The patients were divided into two groups: group 1 (n = 45), received basic therapy; group 2 (n = 33), in addition to basic therapy, received the bacterial vaccine Immunovac-VP-4 according to a combined scheme. The biomaterial sampling was carried out by scraping of epithelial cells from the nasal mucosa, pharyngeal scraping and salivary gland secretion on days 1, 14 and 30 of the study. sIgA levels in all biological fluids were studied using ELISA technique (JSC Vector-Best, Russia).
14 days after the start of observation, the dynamics of sIgA levels in nasal scrapings in group 1showed a significant decrease relative to the baseline values (p = 0.02), whereas the level of sIgA remained unchanged during the specified period (p = 0.07) in the group of patients receiving, along with basic therapy, additional Immunovac-VP-4 treatment. The dynamics of sIgA level in pharyngeal scrapings in the group of patients receiving only basic therapy did not change throughout the study period. Menwhile, the group of patients receiving basic therapy supplemented with Immunovac-VP-4 showed a significant increase in sIgA levels by the 30th day of follow-up over the baseline values (p = 0.02). The level of sIgA in salivary gland secretions did not differ significantly between the study groups during the entire follow-up period.
The results of our study showed that, in order to assess the state of mucosal immunity in patients with COVID-19, one may recommend determination of sIgA in nasal secretions. The Immunovac-VP-4 prescribed in complex therapy is accompanied by an increase in the sIgA levels at the mucous surfaces of the respiratory tract.
{"title":"Secretory IgA in patients with COVID-19 at different regimens of using multicomponent vaccine Immunovac-VP-4","authors":"M. P. Kostinov, N. D. Abramova, V. N. Osiptsov, V. R. Tatevosov, V. V. Gainitdinova, N. O. Kryukova, I. A. Baranova, E. A. Khromova, Elena S. Korovkina, A. G. Chuchalin, O. A. Svitich, K. V. Mashilov","doi":"10.46235/1028-7221-13541-sii","DOIUrl":"https://doi.org/10.46235/1028-7221-13541-sii","url":null,"abstract":"The mucosal immunity performs an important function in prevention of respiratory infections including COVID-19. The search for approaches to activate the synthesis of post-infectious antibodies by correcting the factors of innate and adaptive immunity at mucous membranes of respiratory tract in patients with infection caused by the new coronavirus may be relevant for the treatment of patients with COVID-19. The aim of our study was to assess the concentrations of sIgA in the upper respiratory tract in patients with a confirmed diagnosis of Coronavirus infection caused by the COVID-19, and to evaluate the effect of an immunostimulating drug of bacterial origin upon the sIgA secretion.
 The patients were divided into two groups: group 1 (n = 45), received basic therapy; group 2 (n = 33), in addition to basic therapy, received the bacterial vaccine Immunovac-VP-4 according to a combined scheme. The biomaterial sampling was carried out by scraping of epithelial cells from the nasal mucosa, pharyngeal scraping and salivary gland secretion on days 1, 14 and 30 of the study. sIgA levels in all biological fluids were studied using ELISA technique (JSC Vector-Best, Russia).
 14 days after the start of observation, the dynamics of sIgA levels in nasal scrapings in group 1showed a significant decrease relative to the baseline values (p = 0.02), whereas the level of sIgA remained unchanged during the specified period (p = 0.07) in the group of patients receiving, along with basic therapy, additional Immunovac-VP-4 treatment. The dynamics of sIgA level in pharyngeal scrapings in the group of patients receiving only basic therapy did not change throughout the study period. Menwhile, the group of patients receiving basic therapy supplemented with Immunovac-VP-4 showed a significant increase in sIgA levels by the 30th day of follow-up over the baseline values (p = 0.02). The level of sIgA in salivary gland secretions did not differ significantly between the study groups during the entire follow-up period.
 The results of our study showed that, in order to assess the state of mucosal immunity in patients with COVID-19, one may recommend determination of sIgA in nasal secretions. The Immunovac-VP-4 prescribed in complex therapy is accompanied by an increase in the sIgA levels at the mucous surfaces of the respiratory tract.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"83 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136059586","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}
{"title":"[Allied Forum on Immunology. Abstracts. May 31-June 4, 2004, Ekaterinburg, Russia].","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"9 Suppl 1 ","pages":"1-362"},"PeriodicalIF":0.0,"publicationDate":"2004-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25268285","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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