Russian journal of immunology : RJI : official journal of Russian Society of Immunology最新文献

{"title":"Levels of TREC and KREC molecules significance determining in peripheral blood for predicting the outcome of COVID-19 disease in the acute period","authors":"Maria A. Saitgalina, Yu. V. Ostankova, N. A. Arsentieva, Z. R. Korobova, N. E. Liubimova, V. A. Kashchenko, A. N. Kulikov, D. E. Pevtsov, O. V. Stanevich, E. I. Chernykh, Areg A. Totolian","doi":"10.46235/1028-7221-14714-lot","DOIUrl":"https://doi.org/10.46235/1028-7221-14714-lot","url":null,"abstract":"The disease caused by the highly contagious SARS-CoV-2 virus novel coronavirus infection (COVID-19) had killed more than 6.5 million people at the end of December 2022. The severity of the manifestation of the infectious process varies from asymptomatic forms to rapid progression to life-threatening conditions requiring emergency measures. One of the factors, the severity of which affects the outcome of the disease, is lymphopenia, the cause of which may be a violation of lymphopoiesis. The identification of laboratory markers of a high risk of mortality in patients with COVID-19 plays an important role in improving patient care algorithms and increasing their survival. Levels of TREC and KREC molecules in peripheral blood, respectively, can serve as molecular markers of the severity of T and B lymphopenias. The aim of our work was a comparative analysis of the levels of TREC and KREC molecules in the peripheral blood of surviving and deceased patients with COVID-19. The material was whole blood samples obtained from 1745 people, including: 1028 patients diagnosed with novel coronavirus infection (COVID-19) (ICD-10 code U07.1), of which 937 patients recovered and 91 died; 717 apparently healthy individuals (control group). The levels of TREC and KREC molecules were assessed by quantitative multiplex Real-time PCR using the TREC/KREC-AMP PS reagent kit (Federal Scientific Research Institute Pasteur, St. Petersburg). Statistically significant differences in the levels of KREC and TREC molecules between the control group and patients, both surviving and deceased, were established. A significant decrease in median concentrations of KREC molecules was shown in patients with a lethal outcome compared with survivors (p = 0.0019, 95% CI). Among the deceased patients, in 63.7% of cases, the levels of TREC or KREC molecules were reduced relative to the corresponding age norms. Of these, in 20.9% of cases, both analytes were reduced in patients. When assessing the diagnostic significance of the levels of the analytes under study for predicting the outcome of the disease, the area under the AUC curve for KREC was 0.630.029, which indicates the average strength of the prognostic model of the patient's death depending on the level of KREC in the blood. The constructed model is statistically significant (p = 0.002). Monitoring laboratory parameters of patients with COVID-19, including those who died, allows you to determine the prognostic factors that are most significant for assessing the outcome of the disease. Based on the assessment of the KREC level, a predictive model with high specificity reflects the risk of death in patients with COVID-19. Thus, the quantitative determination of the level of KREC molecules in the peripheral blood can be attributed to the methods of preventive personalized diagnostics aimed at improving the survival of patients.","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":"136011092","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":"Indices of cellular and humoral immunity in a patient with a history of central precocious puberty in anamnesis","authors":"Diliara R. Khisamutdinova, Ya. I. Kozlova, E. B. Башнина, E. V. Frolova, A. E. Uchevatkina, L. V. Filippova, N. V. Vasilyeva","doi":"10.46235/1028-7221-13906-ioc","DOIUrl":"https://doi.org/10.46235/1028-7221-13906-ioc","url":null,"abstract":"The etiology of precocious puberty includes organic anomalies, genetic mutations, but the primary cause remains unclear in the vast majority of cases. Gonadotropin-releasing hormone (GRH) agonists are used as a treatment of gonadotropin-dependent precocious puberty. Blocking the secretion of gonadotropin-releasing hormone, these drugs stop the premature development of sexual features, prevent premature closure of ossification zones, thereby increasing the childs expected adult height. The interest in the effects of this group of drugs beyond the hypothalamic-pituitary-gonadal axis has been recently increased. A series of clinical cases have been reported on the development of autoimmune diseases, e.g., autoimmune thyroiditis, Graves disease and type 1 diabetes. The article presents a clinical observation of a patient with central form of premature development who exhibited satisfactory response to treatment with a GRH agonist drug. Further follow-up did not show any reproductive dysfunction. Upon immunological examination, a disturbance was revealed only in the cellular component of immunity. An increased metabolic activity of neutrophils was found, thus, probably, indicating a nonspecific inflammatory process. The levels of immunoglobulins A, M, G matched the reference values. Thus, the therapy with a drug from the group of GRH agonists was effective and safe in terms of influencing the patients immune system. The role of hormonal disorders and effects of GRH agonists on the development of immunopathological conditions require further research.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"54 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":"136059443","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":"Mucosal humoral immune response of respiratory tract in medical workers during the post-COVID-19 period","authors":"N. O. Kryukova, Albina А. Khasanova, I. A. Baranova, M. P. Kostinov, O. A. Svitich, A. G. Chuchalin","doi":"10.46235/1028-7221-13921-mhi","DOIUrl":"https://doi.org/10.46235/1028-7221-13921-mhi","url":null,"abstract":"Currently, the role of local respiratory tract immunoglobulins in COVID-19 and rearrangement of mucosal immune response in the post-COVID period have not been sufficiently studied. Our aim was to evaluate long-term effects of novel coronavirus infection on the mucosal immunity in healthcare workers over the post-infection period.
 A total of 180 healthcare workers, ranging in age from 18 to 65 years, were enrolled in a one-stage, cross-sectional study. The subjects with a history of COVID-19 were divided into three groups, depending on the severity of their disease. The control group consisted of 44 healthcare workers who had no history of novel coronavirus infection. Secretory immunoglobulin A (sIgA) and total immunoglobulin G (IgG) levels were quantified in saliva samples, induced sputum samples, naso- and oropharyngeal scrapings by ELISA technique. Specific anti-SARS-CoV-2 IgG antibodies were quantified in the serum by chemiluminescence immunoassay.
 Numerous shifts in adaptive immune response were detected for different mucosal compartments, i.e., in subjects who suffered from severe or moderate-to-severe COVID-19, salivary sIgA levels were significantly higher than those in the control group (p 0.05 and p 0.005, respectively). An inverse correlation was demonstrated between the levels of total sIgA in all mucosal sites, and the number of days from the onset of disease to the start of study (r = 0.278, р 0.05). When compared to the control subjects, all the patients with prior COVID-19 had significantly higher levels of total IgG in the induced sputum samples. Total IgG in saliva was also higher in the group of patients who had severe infection (p 0.05). By contrast, IgG levels in nasopharyngeal samples were decreased in severe and moderately severe groups compared to the control group, thus, probably, indicating an immunodeficiency state in these cases. A direct significant correlation was also detected between the levels of total IgG in all studied samples and the levels of specific IgG antibodies against SARS-CoV-2 in the serum.
 Long-term changes in the humoral mucosal immune response were most pronounced in the healthcare workers with a history of severe or moderate-to-severe COVID-19.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"10 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":"136059731","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":"Single nucleotide polymorphism of osteoprotegerin as a possible biomarker of rheumatoid arthritis in Bashkir population of Chelyabinsk region","authors":"Yu. V. Chumacheva, Darya S. Stashkevich, I. V. Devald, T. A. Suslova","doi":"10.46235/1028-7221-13964-snp","DOIUrl":"https://doi.org/10.46235/1028-7221-13964-snp","url":null,"abstract":"Rheumatoid arthritis (RA) is a multifactorial autoimmune rheumatic disease of unknown etiology characterized by chronic erosive arthritis. The protein osteoprotegerin (OPG) is a member of bone tissue homeostasis (RANK/RANKL/OPG) which is responsible for the regulation of osteoclast differentiation and osteolysis. The altered binding of RANKL and OPG is one of the causes of many diseases with increased production of pro-inflammatory cytokines, including rheumatoid arthritis. Polymorphic variants of the genes that control protective reactions could affect the level of production for encoded proteins and, thus, changing the course of immune response in RA. G1181C SNP in osteoprotegerin gene leads to disruption of its transcriptional activity and conformation of the protein itself, which can lead to an imbalance of pro- and anti-inflammatory cytokines. We analyzed the relationship between the TNFRSF11B gene polymorphism at the 1181 G C position and the risk of developing RA in the Bashkir population. The analysis was based on a molecular genetic study of single nucleotide polymorphism in groups of patients with rheumatoid arthritis and conditionally healthy individuals of the Bashkir population of the Chelyabinsk Region. Statistical evaluation was carried out using standard criteria generally accepted in immunogenetics. The 1181*GC polymorphism of the osteoprotegerin gene is characterized by interpopulation differences, which confirms the importance of using an ethnically identical comparison group to assess the association with a predisposition to multifactorial pathology. We showed that the carriage of genotype 1181 G/C was increased in the group of Bashkirs with rheumatoid arthritis. This genotype could be considered a biomarker of susceptibility to RA. No differences in the SNP allelic frequencies and genotypes were found among women with RA. Our research is a part of comprehensive assessment of the interaction of cytokines and their receptors from the TNFsuperfamily as an immunogenetic component of RA genesis.","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":"136059735","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":"Immunological and biochemical markers of adverse outcome in COVID-19 and arterial hypertension","authors":"Anna V. Mordyk, N. V. Bagisheva, M. V. Moiseeva, E. P. Antipova, V. V. Streltsova","doi":"10.46235/1028-7221-13945-iab","DOIUrl":"https://doi.org/10.46235/1028-7221-13945-iab","url":null,"abstract":"Coronavirus is able to affect various organs and systems including the immune system. At the same time, the state of the immune system may be initially changed in patients with pre-existing comorbid non-infectious disorders. The aim of our study was to evaluate biochemical and immunological markers of adverse outcomes in the patients with new coronavirus infection with underlying arterial hypertension.
 The retrospective study included 47 patients with COVID-19 and arterial hypertension, who underwent a study of C-reactive protein (CRP), interleukin-6 (IL-6), assessing the increased values of these markers and the outcomes of the disease. The study group included 23 male and 24 female patients at the median age of 54 (for men), and 57 years old (for women).
 Upon admittance of the patients with COVID-19 and hypertension to the hospital, a parallel increase in both CRP and IL-6 was registered in these cases. Statistically significant differences were found in the levels of CRP and IL-6 in patients with a favorable versus unfavorable clinical outcomes. The levels of CRP and IL-6 in deceased patients were higher and did not tend to decrease. Thus, the simultaneous increase in CRP and IL-6 in patients with COVID-19 and hypertension is considered an unfavorable prognostic parameter for patients survival.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"33 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":"136059278","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":"Therapeutic effect of a new immunotropic composition tested in the model of periodontitis in experimental animals","authors":"K. A. Khlystova, N. S. Chumakov, N. G. Sarkisyan, Natalia N. Kataeva, L. I. Drozdova, I. A. Tuzankina","doi":"10.46235/1028-7221-13532-teo","DOIUrl":"https://doi.org/10.46235/1028-7221-13532-teo","url":null,"abstract":"The article deals with usage of a novel immunotropic drug composition in experimental model of periodontitis. The composition contains silicoorganic glycerogel, exhibits broad spectrum of action upon the etiological pathogen. A good therapeutic effect was revealed by clinical, laboratory and histological criteria. Histology showed absence of osteoclasts, reduced lacunas, higher density and normalization of tissue structures, recovery of microcirculation, angiogenesis and formation of granulation tissues. However, the phosphorus-to-calcium ratio in the group supplied with peroral vitamin D treatment, was characterized by significant decrease in alkaline phosphatase and inorganic phosphorus thus confirming efficiency of complex topical effect of the given composition and vitamin D.","PeriodicalId":21507,"journal":{"name":"Russian journal of immunology : RJI : official journal of Russian Society of Immunology","volume":"23 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":"136059280","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":"Clinical and immunological efficacy of the immunomodulating hexapeptide arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine in the complex postoperative treatment of children with acute osteomyelitis","authors":"Galina A. Chudilova, E. A. Chicherev, Yu. V. Teterin, V. N. Chapurina, V. A. Tarakanov, N. K. Barova, I. V. Nesterova","doi":"10.46235/1028-7221-13763-cai","DOIUrl":"https://doi.org/10.46235/1028-7221-13763-cai","url":null,"abstract":"The recurrent and persistent nature of osteomyelitis, like as associated high morbidity of patients, prolonged hospitalization and expensive treatment require development of new approaches in therapy and pathogenetic justification of the immunotropic drugs usage in complex etiopathogenetic treatment of this disorder. Our objective was to evaluate the clinical and immunological efficacy of hexapeptide (HP), arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine implemented in the complex treatment of acute osteomyelitis in children during the postoperative period. 19 children aged 8-15 years with acute osteomyelitis (AOM) were studied: the study group 1 (SG1, n = 11) received a standard treatment at all the disease stages; in study group 2 (SG2, n = 8), the standard therapy was supplemented with a medical drug Imunofan, containing hexapeptide (НP) as the active substance. Prior and after the course of drug treatment, we determined the following parameters: the contents of T cells (CD3+CD19-, CD3+CD4+, CD3+CD8+, CD3+CD4+/CD3+CD8+) and B cells (CD3-CD19+), NK (CD3-CD16+CD56+) by means of Cytomics FC-500 (Веckman Coulter, USA), the levels of serum IgA, IgM, IgG (ELISA tests), assessment of phagocytic activity of neutrophil granulocytes (NG) with determining the ratio of actively phagocytic NG (%PhAN), capture processes (PhN, PhI) and the completeness of phagocytosis (%D, DI) tested with S. aureus (strain No. 209). In the studied groups with AOM, a decreased content of T lymphocytes, T helper cells, T lymphocytes, NK cells was revealed, along with unchanged content of B lymphocytes. In SG2, the increased IgA and IgG levesl have been shown. We have also revealed a deficiency of phagocytic function associated with the processes of phagocytosis completion. The use of immunomodulatory therapy with an HP-containing pharmaceutical drug in combination with standard treatment was associated with restoration of immunological parameters to the reference values of healthy children, thus leading to shorter febrile period, milder manifestations of intoxication, earlier periods of reconvalescence from purulent-inflammatory process, and reduced hospital stay. The obtained positive clinical and immunological effects demonstrate the expediency of targeted immunomodulatory therapy including a pharmaceutical HP-containing drug as the active substance in the complex postoperative treatment of children with AOM. Restoration of the disturbed mechanisms of anti-infectious immunity in AOM under usage of immunomodulating HP contributes to more effective elimination of pathogens and, as a result, improvement of the clinical course of the disease, as well as prevention of chronic inflammatory processes and aggravation of immune system dysfunction.","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":"136059282","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":"Time-dependent changes of platelet and D-dimer parameters in vaccinated <i>versus</i> non-immunized COVID-19 patients","authors":"M. P. Kostinov, Chen Zhang, I. A. Khrapunova, A. S. Pechenik, V. A. Utkin, M. N. Loktionova, K. V. Mashilov, Irina L. Soloveva","doi":"10.46235/1028-7221-13983-tdc","DOIUrl":"https://doi.org/10.46235/1028-7221-13983-tdc","url":null,"abstract":"There are increasing data concerning changes in hematological (clinical) and biochemical blood tests in patients with COVID-19 infection, which indicate the severity of the manifestations of the infectious process. Coagulopathy often correlates with the severity of COVID-19 disease and the risk of death. In this regard, prediction of developing coagulopathy and its prevention remain quite relevant. The aim of our study was to identify differences in the content of platelets and D-dimer in patients with COVID-19. The study included cohorts of patients vaccinated against SARS-CoV-2, and those not immunized against this infection.
 A prospective, randomized, observational study of the patients response was performed in cohorts of 588/52.2% vaccinated (vaccinated) and 588/52.2% non-immunized (non-vaccinated) patients with diagnosed COVID-19 over the period from 23.06.2021 to 01.05.2022. The levels of blood platelets and D-dimer, as well as clinical outcomes of the disease in patients with COVID-19, were studied in dynamics on days 1-2, 5-6 and 10-12 of hospitalization.
 Upon admission, the normal value of the blood platelet counts did not differ between the compared groups, being 206.58 109 in vaccinated group and 204.85 109 in the unvaccinated group, respectively. a moderate increase in the concentration of D-dimer was noted in both groups upon admission, i.e., 2838.60 ng/mL in the group of vaccinated patients and 3242.08 ng/mL among the unvaccinated patients. In the course of the study, we have shown that the dynamics of D-dimer index in vaccinated versus non-immunized persons was similar according to the days of disease, showing an increase from the first day and a trend towards an higher values, starting from 5-6 days. At the same time, the dynamics in the vaccinated patients was somewhat less favorable than that of the non-immunized subjects. In the patients who were not immunized throughout the entire observation period, the platelet count exceeds the levels found in vaccinated subjects, thus suggesting higher risk of thrombosis and cytokine storm.
 The data obtained show that the dynamics of D-dimer and platelet counts in vaccinated and non-immunized people is similar on appropriate terms of the illness. However, the changes are more pronounced in vaccinated cohort, but it does not indicate a greater risk of adverse outcomes.","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":"136059434","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":"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}

{"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}