Medical Immunology (Russia)最新文献

{"title":"IL-4 and its polymorphism (IL4-589C/T) in cervical neoplasia","authors":"T. Abakumova, I. Myagdieva, D. Dolgova, S. Gening, I. Antoneeva, T. Gening","doi":"10.15789/1563-0625-iai-2691","DOIUrl":"https://doi.org/10.15789/1563-0625-iai-2691","url":null,"abstract":"The transition of cervical neoplasia (CIN) to cervical cancer occurs with the active participation of IL-4, for which both pro- and antitumor effects have been shown with tumors of various localizations. The expression of cytokines is regulated at the transcriptional level in the promoter region of the gene. It has been shown that the genotype IL4 (589C/T) (rs2243250) is associated with the development of gastric and breast cancer. The contribution of IL-4 genotypic variations to the development of CIN has not yet been studied. The aim of the study was to assess the risk of developing cervical neoplasia by the presence polymorphism of IL4 (589C/T) and the level of IL-4. The object of the study was circulating neutrophils, serum and genomic DNA of 36 patients with CIN and 20 women without dysplasia (comparison group). Using ELISA, the level of IL-4 was determined in neutrophil lysate and serum. Phagocytic activity and adhesive ability (CD11b) of neutrophils were assessed. Allele-specific real-time PCR using Taq-Man probes was used to analyze of the IL4 589C/T (rs2243250). Statistical processing was carried out using Statistica 13 and Jamovi 1.6.5.0. As a result of the study, it was found that the level of IL-4 in serum and circulating neutrophils in patients with CIN is significantly higher than in the comparison group. The -589C* allele of the IL4 gene and the TT genotype are more common in the group with CIN (55.5%) than in the control (25%). At the same time, a direct relationship was established between the presence of polymorphism and increased adhesive ability and with indicators of the phagocytic number of circulating neutrophils. Analysis of the incidence of IL4 C589T by the «case-control» method showed that the chances of CIN formation in carriers of the -589C allele and the TT genotype were 3.75 (95% CI: 1.013 - 13.880, Chi-square = 4.161, p = 0.042). The -589C* allele and TT IL4 genotype, neutrophil and serum IL-4 levels are associated with HPV infection. Using a binary logistic regression model, we demonstrated the possibility of using IL-4 levels in circulating neutrophils and IL-4 gene polymorphism (589C/T) for the differential diagnosis of patients with CIN (χ2 = 15.6, p = 0.001). Significant significance for their combination was assessed by ROC-curve analysis (IL-4 in neutrophils; IL4 (-589С*), 75% probability. Thus, the IL4 (589C/T) is associated with the adhesive and phagocytic activity of circulating neutrophils. In HPV-infected patients, IL4 gene polymorphism (589C/T) can serve as a marker for early detection and prognosis of CIN.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83848433","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":"Hypersegmentation of neutrophil nuclei in peripheral blood of patients with localized and advanced cancer of the larynx and laryngopharynx","authors":"E. Kologrivova, R. Pleshko, O. Cheremisina, M. Boldyshevskaya","doi":"10.15789/1563-0625-hon-2715","DOIUrl":"https://doi.org/10.15789/1563-0625-hon-2715","url":null,"abstract":"Neutrophilic granulocytes have a wide spectrum of functional activity. In recent years, the functional significance of neutrophils in the development and course of malignant neoplasms has been discussed. It has been shown that neutrophilic granulocytes can play pro- or antitumor activity. The aim of the study was to assess the structural and functional features of neutrophils in patients with varying degrees of prevalence of cancer of the larynx and laryngopharynx. Forty-one patients (aged 35-67) with newly diagnosed cancer of the larynx and laryngopharynx were examined and divided into subgroups according to the TNM classification: the first subgroup (14 patients) with a localized tumor process consisted; and the second subgroup (27 patients) with a widespread tumor process. The relative and absolute number of neutrophils was assessed, and the neutrophil-lymphocyte ratio (NLR) was determined. The content of neutrophils with varying degrees of nuclear segmentation in the blood was calculated, the activity of myeloperoxidase, cationic proteins, alkaline phosphatase, and the degree of neutrophil activation in the NBT test was determined cytochemically. Concentration of interleukin-8 was determined using ELISA. In patients with cancer of the larynx and laryngopharynx the number of neutrophils (p = 0.045) and NLR (p = 0.033), as well as serum concentration of interleukin 8 (p = 0.011), increased compared to healthy individuals. The proportion of cells with hypersegmented nuclei in the neutrophil population (p < 0.001) and cytotoxic potential increased with the spread of tumor process. A direct correlation (r = 0.42, p = 0.03) was found between the T index, which reflects the volume of the tumor, and the content of hypersegmented neutrophils. It can be argued that such a simple and accessible laboratory parameter as the degree of segmentation of the nuclei of neutrophilic granulocytes can be used as one of the criteria to assess and predict the course of the tumor process.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72519871","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":"HDL apoprotein immunization induces T cell-mediated venulitis and inflammation in aorta","authors":"А. Y. Sidorov, K. Fomina, L. Beduleva","doi":"10.15789/1563-0625-hai-2699","DOIUrl":"https://doi.org/10.15789/1563-0625-hai-2699","url":null,"abstract":"The hypothesis that atherosclerotic processes are mostly caused by immune (autoimmune) mechanisms has recently been gaining attraction. At the same time, the autoimmune hypothesis of atherogenesis has not become generally accepted and requires additional evidence. Previously, we were able to induce changes in the aortic wall similar to those observed in the early stages of human atherosclerosis, and also to produce visceral obesity in normocholesterolaemic Wistar rats by a single immunization with human native high- or low-density lipoproteins. We also found that the immune response to native human HDL causes atherosclerosis-like lesions in the rabbit aorta, such as adipocyte and chondrocyte metaplasia, proteoglycan deposits, and leukocyte infiltration. Atherosclerosis-like lesions developed in the aorta of hnHDL-immunized rabbits against a background of normal blood LDL-cholesterol level. Thus, an immune response against HDL or LDL may be an independent cause of atherogenesis. The aim of this study was to test whether immunization with human HDL apoproteins (apoA1 and apoE proteins) would induce atherosclerosis-like lesions in the aorta of normocholesterolemic Wistar rats. HDL apoproteins were isolated from human or rat plasma. Wistar rats (n = 5) aged 2 months were used for immunization with human HDL apoproteins. HDL apoproteins were administered as a single intradermal injection of 100 mg per rat in incomplete Freund’s adjuvant. Control rats were injected subcutaneously with incomplete Freund’s adjuvant (n = 5). Rats were dissected 25 weeks after immunization. Rat aorta sections were stained with hematoxylin and eosin for light microscopy. T lymphocytes infiltration was determined by immunohistochemical staining with FITC-labeled antibodies specific to rat CD3. CD3+T lymphocytes were detected using an Olympus BX53 fluorescent microscope. The level of antibodies to human and rat HDL apoproteins was determined by indirect enzyme-linked immunosorbent assay. Immunization with HDL apoproteins induced a T cell mediated immune response without production of autoantibodies to HDL apoproteins. The aortic intima and adventitia were infiltrated with T lymphocytes in rats immunized with HDL apoproteins. Pronounced T lymphocytic infiltration was found in all layers of the vein wall in rats immunized with human HDL apoproteins. Thus, immunization with HDL apoproteins causes T cell mediated inflammation of the aorta and venulitis.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75330279","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":"Immunomodulatory and neurotropic activities of synthetic peptides in a model of brain injury in rats","authors":"N. B. Serebryanaya, S. N. Shanin, T. A. Filatenkova, E. Fomicheva, A. S. Komlev, O. Shamova","doi":"10.15789/1563-0625-ian-2754","DOIUrl":"https://doi.org/10.15789/1563-0625-ian-2754","url":null,"abstract":"Treatment of consequences of traumatic brain injury (TBI) remains one of the current problems of medicine. To increase the effectiveness of treatment of post-traumatic complications, various drugs are recommended, including the peptide with neuromodulatory activity Semax.The present study aims to determine the presence of neuro- and immunoprotective properties of the synthetic peptide PR5, composed of fragments of proline-rich antimicrobial peptides.The work was performed on male Wistar rats weighing 300-350 g. The “falling weight” model of mechanical brain injury was used, which mainly causes diffuse brain damage. The synthesized peptide PR5, composed of fragments of known proline-rich peptides of animal neutrophils, and the peptide preparation Semax in the form of a 1% aqueous solution were used. The drugs were administered intranasally 1 hour after TBI, then twice a day for 4 days at a dose of 100 mg/kg body weight. Control animals received physiological saline in the same regimen as the peptide preparations.TBI led to a significant decrease in body weight, but in rats receiving the peptide preparation Semax, the decrease in body weight was significantly less than in control animals, and the PR5 preparation completely prevented the decrease in body weight after TBI. After TBI, the proliferative activity of lymphocytes was suppressed and the cytotoxicity of NK cells decreased. In animals treated with peptide preparations, there was no significant suppression of NK cell cytotoxicity, and the proliferative activity of lymphocytes was restored to the level of control animals by day 14 after TBI. Both peptide preparations used contributed to higher locomotor activity, and in animals treated with the PR5 peptide, this type of activity reached the parameters of control animals. The reduction in freezing duration in groups treated with peptide preparations indicates the presence of a sedative effect.The peptide preparation PR5 was active in this series of experiments, showing immunotropic and neuroprotective activity comparable to the Semax preparation. Further studies aimed at confirming the identified types of activity of the peptide preparation PR5 may justify its prospects for clinical use as a new nootropic agent.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80209873","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":"MDC/CCL22 depletion in COVID-19 and post-COVID","authors":"Z. Korobova, A. Totolian","doi":"10.15789/1563-0625-mcd-2804","DOIUrl":"https://doi.org/10.15789/1563-0625-mcd-2804","url":null,"abstract":"In this article, we explore the role of macrophage-derived chemokine (MDC/CCL22) in COVID-19 immunity. The study included plasma samples of 289 patients with PCR-verified COVID-19 from specialized hospitals. The blood samples were collected at admission, approximately 7 days after the start of infection. Genetic testing of the virus was performed in nasopharyngeal swabs to determine the viral strain for each patient. We also included blood plasma of 69 convalescent patients who had recovered from COVID-19 more than a month prior to the study. Additionally, 51 healthy donors were included in the study as controls. The concentrations of MDC/CCL22 and other cytokines and chemokines were measured with multiplex analysis using Luminex MagPix Technology. The results showed that COVID-19 patients had significantly lower MDC levels in their plasma, regardless of the SARS-CoV-2 strain, compared to healthy donors. This finding suggests that MDC/CCL22 depletion may play a role in COVID-19 immunity. Furthermore, convalescent patients still showed decreased concentrations of MDC/CCL22 more than a month after infection, indicating that this depletion may persist even after recovery. We propose two mechanisms that can explain the reasons leading to MDC/CCL22 depletion. The first is binding and inactivation of this chemokine with SARS-CoV-2 peptides, making it not only undetectable for commercial kits, but also less functionally active. Another mechanism is the dysfunction of its effector cells (e.g., DCs and macrophages). Lymphopenia following COVID-19 can potentially be explained by the absence of MDC/CCL22. This may lead to a shift towards hyperactivation in the inflammatory response, potentially explaining the severity of COVID-19. This research sheds light on the importance of MDC/CCL22 in COVID-19 immunity and highlights the need for further investigation into its role in the disease. Understanding the mechanisms behind MDC/CCL22 depletion could provide new insights into the pathogenesis of COVID-19 and inform the development of potential treatments.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80245390","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":"Study of the immunoglobulin and oxidized protein content of semen under infertility","authors":"N. V. Vavilov, A. P. Godovalov","doi":"10.15789/1563-0625-sot-2850","DOIUrl":"https://doi.org/10.15789/1563-0625-sot-2850","url":null,"abstract":"Among the causes of male infertility, enough attention is paid to oxidative stress, which in turn is a pathogenetic link in the inflammatory process. However, there is practically no information on the content of oxidized modified proteins in the semen, which makes it difficult to study the pathogenesis of diseases of the male reproductive system. In part, protein oxidation may be due to the production of reactive oxygen species by microorganisms, both directly and indirectly through the activation of immune system cells. The aim of the research was to study the level of oxidized modified proteins and changes in immunoglobulin concentrations in the semen under bacteriospermia. A study was made of the ejaculate of 48 men who applied to the clinic for infertility in marriage. The comparison group consisted of 32 practically healthy men who had no growth of microorganisms in the ejaculate samples. When conducting bacteriological analysis, the studied samples were diluted 10 times and used the generally accepted method. The concentration of albumin, immunoglobulins A, M, G, E was determined in the spermatic fluid. The oxidative modification of proteins was evaluated in the reaction with 2,4-dinitrophenylhydrazine. The concentration of oxidized proteins was expressed in nmol/mg of the total protein of the studied biological fluid. The biuret method was used to determine the protein concentration. Statistical analysis of the results was performed using descriptive statistics and Student's t-test for paired data. The concentration of protein in the seminal fluid did not differ significantly among the studied groups. The albumin concentration (16.96±1.28 mg/mL) was statistically significantly lower in the absence of microorganism growth than in bacteriospermia. With bacteriospermia, a decrease in the concentration of IgM and IgA and an increase in the level of IgG were noted. The degree of protein oxidation is maximum when enterobacteria are isolated from seminal fluid. Thus, during the studies it was found that, despite the absence of a clinic, with asymptomatic bacteriospermia, the secretion of immunoglobulins G into the semen is observed. The accumulation of oxidized proteins in the seminal fluid in bacteriospermia has been shown.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77128922","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":"Myeloid-derived suppressor cells as biomarkers of the effectiveness of therapy with new biological agents in axial spondyloarthritis","authors":"T. Tyrinova, A. Morenkova, A. V. Fedorova, M. Tikhonova, N. Ilina, O. Chumasova, A. Sizikov","doi":"10.15789/1563-0625-mds-2696","DOIUrl":"https://doi.org/10.15789/1563-0625-mds-2696","url":null,"abstract":"Innate immune cells, including myeloid cells — myeloid derived suppressor cells (MDSCs) — are supposed to play an important role in the pathogenesis of axial spondyloarthritis (AxSp). Myeloid derived suppressor cells represent a heterogeneous population of immature cells capable of suppressing innate and adaptive immune responses with the most pronounced suppressor activity against T cells. Biological disease-modifying antirheumatic drugs (bDMARDs) can reduce the clinical and laboratory disease activity, but their effectiveness varies widely in different patients with AxSp. The present study is aimed at studying MDSCs subpopulations and their suppressive function depending on the response to bDMARD therapy in AxSp. The study included AxSp patients with a disease duration of 16.5 years (median); HLA-B27 (+) status was detected in 79% of cases. All patients received bDMARDs at least the past 12 weeks, including TNF inhibitors (etanercept, certolizumab pegol, adalimumab, or golimumab) or IL-17 inhibitors (secukinumab, ixekizumab, or netakimab). Percentage of granulocytic MDSCs (G-MDSCs, Lin-HLA-DR-CD33+CD66b+), monocytic MDSCs (M-MDSCs, HLA-DRlow/-CD14+), MDSCs of early stage differentiation (E-MDSCs, Lin-HLA-DR- CD33+CD66b-), as well as intracellular expression of arginase-1 was assessed by flow cytometry. Frequency of circulating MDSC subpopulations of patients with a stable response to bDMARDs (responders) did not differ significantly compared to healthy donors. Patients not responding to bDMARDs therapy showed increased relative and absolute number of E-MDSCs compared to healthy donors (pU = 0.01 and pU = 0.02, respectively) and the responders (pU = 0.03 and pU = 0.07, respectively). Increased percentage of E-MDSCs was positively correlated to disease activity — ESR (Rs = 0.821; p = 0.023), CRP (Rs = 0.714; p = 0.07) and ASDASCRP (Rs = 0.829; p = 0.042) in the non-responder group. Responder patients exhibited no correlation between disease activity and circulating MDSCs. The suppressor potential of MDSCs was analyzed by the intracellular expression of arginase-1 molecule which is involved in the inhibition of T cell response. Patients with the stable response were characterized by increased expression of arginase-1 in E-MDSCs compared to donors (pU = 0.02). Non-responders did not demonstrate significant changes in Arg-1 expression, however, the percentage of arginase-1-expressing G-MDSCs was positively correlated to indexes ASDASESR (Rs = 0.857; p = 0.014) and BASDAI (Rs = 0.785; p = 0.036). Thus, E-MDSCs as well as arginase-1 expression in MDSCs may serve as biomarkers of effectiveness bDMARD therapy, and act as potential candidate predictors of response to therapy in AxSp.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86279007","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":"PD-L1 and PD-L2 gene expression in human glioblastoma cells resistant to chemo- and radiotherapy","authors":"A. A. Pinevich, N. L. Vartanyan, L. Kiseleva, I. I. Bode, I. Y. Krutetskaya, A. V. Kartashev, V. E. Makarov, T. E. Poneza, I. Smirnov, M. P. Samoilovich","doi":"10.15789/1563-0625-pla-2693","DOIUrl":"https://doi.org/10.15789/1563-0625-pla-2693","url":null,"abstract":"Membrane molecules PD-L1 and PD-L2, ligands of T lymphocytes PD1 receptor, perform immunoregulatory functions. Their binding to the receptor leads to inhibition of proliferation, reduction of cytokine production, cytotoxic response, and apoptosis of T lymphocytes. The cells of many tumors, regardless of their histogenesis, express PD-L1 molecules, thus limiting the development of an anti-tumor immune response. Glioblastomas are highly malignant recurrent tumors of the central nervous system. The main sources of glioblastoma recurrence are resistant tumor cells initially present in gliomas with heterogeneous cellular composition, as well as resistant cells that are formed during therapy. Increasing the dose of cytostatic drugs or radiation during relapse therapy is not effective in glioblastomas. It has been shown for a number of tumors, including ovarian cancer and non-small cell lung cancer, that drugs preventing PD-L1/PD1 interaction are effective in the treatment of neoplasms resistant to chemo- and radiotherapy. Immunotherapy using drugs that inhibit the binding of PD-L molecules to their receptor is considered as a way to overcome the resistance of glioblastomas to therapy. The aim of this work was to assess the level of PD-L1 and PD-L2 gene expression in resistant glioblastoma cells lines A172, R1, T2 and T98G, which resumed proliferation after exposure to the maximum for each line, sublethal doses of cytostatic drugs (fotemustine and temozolomide), fractionated or single gamma irradiation. A172 line belongs to glioblastomas that are highly sensitive to these influences, T98G is a highly resistant cell line, while R1 and T2 lines occupy an intermediate position. In intact glioblastoma A172, R1, and T2 cells the level of PD-L1 and PD-L2 gene expression was equally high, while in T98G cells it was significantly lower. Exposure of A172 and R1 glioblastoma lines to cytostatic drugs or irradiation did not significantly change the level of PD-L1 and PD-L2 genes expression typical for intact cells. In T2 glioblastoma cells, and especially in T98G cells, a significant increase in expression of these genes was found, most pronounced for PD-L2 gene. This increase in expression may indicate an enhanced malignancy of resistant T2 and T98G cells. High expression of the genes responsible for the production of PD-L1 and PD-L2, which limit the cytotoxic response against tumor cells, is a prerequisite for the use of drugs targeted against PD-L1 and PD-L2 for the elimination of resistant cells in glioblastoma.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87426139","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":"Attempt to assess direct interactions between tumor burden, myeloid-derived suppressor cells and PD-1- and TIM-3-expressing T cells in multiple myeloma patients","authors":"E. Batorov, T. Aristova, N. Pronkina, V. Denisova, S. Sizikova, G. Ushakova","doi":"10.15789/1563-0625-ato-2760","DOIUrl":"https://doi.org/10.15789/1563-0625-ato-2760","url":null,"abstract":"The avoidance of immune surveillance by malignant plasma cells (PCs) in multiple myeloma (MM) is mediated by different mechanisms, among which an induction of T cell exhaustion and expansion of myeloid-derived suppressor cells (MDSCs) appear to play substantial roles, but it is still a lack of data on possible MDSC-mediated induction of T cell exhaustion. The aim of the present work was to evaluate possible relationship between frequencies of MM PCs, MDSCs and phenotypically exhausted PD-1+ and TIM-3+ T cells in bone marrow (BM) samples and peripheral blood (PB) of MM patients at various disease stages. Peripheral blood (n = 88) and BM samples (n = 56) were obtained from MM patients (newly diagnosed (n = 6), patients in remission (n = 71) and with progressive disease (n = 11)). Frequencies of T cells expressing checkpoint receptors PD-1 and TIM-3, polymorphonuclear MDSCs (PMN-MDSCs, Lin-CD14-HLA-DR- CD33+CD15+/CD66b+), monocyte MDSCs (M-MDSCs, CD14+HLA-DRlow/-), early MDSCs (E-MDSCs, Lin-HLA-DR-CD33+CD15-/CD66b-), and MM PCs (CD45dimCD38+CD138+CD56+CD19-CD117+CD27- CD81-) were assessed with flow cytometry. Circulating and BM-resident PD-1+/TIM-3+T cell subsets, BM E-MDSCs, as soon as MM PCs and serum beta2-microglobulin (B2-M) levels were gradually increased in patients at different stages. Despite that, there were no associations between the markers of tumor load and the studied cell subsets. In patients in remission, BM PMN-MDSCs negatively correlated with CD4+T cells, CD4+PD-1+ and CD8+TIM-3+T cell subsets; there were positive correlations between BM E-MDSCs and CD4+PD-1+TIM-3+ cells and PB M-MDSCs and CD8+PD-1+ and (as a trend) CD8+TIM-3+T cells. We found no associations for the samples of patients at diagnosis and with progression. We can conclude that a possible mutual influence of malignant PCs, MDSCs and PD-1+/TIM-3+T cells is nonlinear, especially during a manifest tumor growth at diagnosis and progression. The detected negative correlations between resident PMN- MDSCs and T cell subsets might be associated with MDSC suppressive function, affecting both predominantly activated PD-1+ cells and exhausted TIM-3+ subsets. The positive correlations between BM E-MDSCs and CD4+PD-1+TIM-3+ cell subset and circulating M-MDSCs and PD-1+ and TIM-3+ CD8+T cells might confirm an ability of MDSCs to induce T cell exhaustion.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85881915","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 characteristics of medical students depending on the duration and program of study","authors":"S. A. Chebotov, R. T. Urazmambetov, I. Andreeva, M. Kharitonova","doi":"10.15789/1563-0625-cai-2753","DOIUrl":"https://doi.org/10.15789/1563-0625-cai-2753","url":null,"abstract":"Chronic psycho-emotional stress can cause dysfunction of neuroimmunoendocrine dysregulation with consequences in the form of a violation of the functional potential of the immune system. Adaptation to new living conditions at the start of studies at a medical university is one of the inevitable circumstances that first-year students overcome. Education under the military training program at a medical university carries an additional stress load in this aspect. Research on the mechanisms of formation of adaptive reactions of the immune system during training under the military training program for officers of the medical service is of undoubted interest. The purpose of the study was to compare the clinical manifestations of immune-mediated pathology and the parameters of adaptive and innate immunity of medical students depending on the length of service and training program. Under observation were 104 medical students, all men, of which 37 were first-year students and 67 were third-year students of a medical university. The subjects of each course were divided into two subgroups depending on the training program. The group of first-year students consisted of 18 people from the military training center (VTC) and 19 people from the medical and preventive faculty (LPF). Among the third-year students of the VUC – 31, LPF – 36. For the clinical characterization of the incidence during the year of study, registration cards for the analysis of immune-mediated pathology were used, the parameters of the immune system at the end of the spring semester were studied using standard methodological approaches. The data obtained indicate that in the first year students with an additional load in the form of a military training program have a more difficult time adapting to learning in comparison with first-year students of the medical faculty. These differences consist in a more frequent and significant clinical manifestation of infectious pathology and are reflected in the functional potential of cellular parameters of innate immunity. The statement of signs of inhibition of the functional potencies of macrophage cells and natural killers in firstyear students of a military training center is an alarming factor in the possible disruption of the adaptive reserves of the immune response system, which probably suggests the need to develop programs to prevent the negative impact of stress-forming factors. By the third year of study, the students of the military training center have the best clinical and immunological indicators of the functioning of the immune system in comparison with the students of the standard educational program of general practitioners. It is likely that during this period the process of psychological adaptation of military medical students is completed.","PeriodicalId":37835,"journal":{"name":"Medical Immunology (Russia)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85166408","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}