Local Immune Status Research Articles

Influence of a combination of dimephosphone and xymedon on the state of local immunity of the oral cavity

The effect of the combination of ultraphoresis of 15% dimephosphone aqueous solution and administration of xymedone on the local immunity state of oral cavity in combined prevention of dental caries is estimated. The used treatment promotes reliable improvement of the local immunity indicators of oral cavity.

尿のユニークな役割 －動物の腎臓病を知らせ、組織局所の免疫を変化させる体液－

尿のユニークな役割 －動物の腎臓病を知らせ、組織局所の免疫を変化させる体液－

Circulating extracellular vesicles carrying Firmicutes DNA reflect the local immune status and may predict clinical response to cancer immunotherapy in urothelial carcinoma

Circulating extracellular vesicles carrying Firmicutes DNA reflect the local immune status and may predict clinical response to cancer immunotherapy in urothelial carcinoma

The influence of parenteral influenza vaccination on local immunity indices and microbiota of oropharyngeal secretion in patients with chronic inflammatory diseases of the upper respiratory tract

When studying the effect of vaccines against influenza, attention is mainly paid to obtaining high titers of protective antibodies in the blood and reducing the incidence of respiratory infections among vaccinated people. At the same time, the changes occurring in patient,s body from the factors of local specific and innate immunity remain insufficiently studied. The aim of the study was to determine the effect of parenteral influenza vaccination on the state of local immunity, cytology and microbiota of oropharyngeal secretion (OS) in patients with chronic inflammatory diseases of the upper respiratory tract. The study of immunological and microbiological parameters was performed in 32 patients with chronic inflammatory diseases of the upper respiratory tract, including 11 diagnosed with chronic rhinosinusitis, 9 – with chronic tonsillitis, 12 – with chronic pharyngitis, 3 and 12 weeks after vaccination with trivalent inactivated influenza-vaccine (PASTEUR, SA, France), which was administered intramuscularly. Single vaccination against influenza A and B has been shown to normalize reduced local humoral immunity indices, in particular sIgA and immune complexes concentrations, increase lymphocyte output to oropharyngeal secretions and cause a significant decrease in the representation of OS transient microflora without affecting the overall level of bacterial contamination. In both periods after the vaccination the reduced content of interferon-α in the OS of patients with chronic inflammatory diseases of the upper respiratory tract did not change. The obtained data allow to recommend vaccination against influenza virus in the period up to 3 months before the the beginning of mass infections as an effective means of stimulating the protective reactions of local immunity of oropha­rynx and nasopharynx mucous membranes in patients with chronic inflammatory diseases of the upper respiratory tract.

Placental-Cadherin, a biomarker for local immune status and poor prognosis among patients with tongue squamous cell carcinoma.

The prognostic and clinicopathological value of placental-Cadherin (CDH3) in multiple cancers is controversial. The diagnostic significance and functional mechanism of CDH3 in tongue squamous cell carcinoma (TSCC) have not been thoroughly investigated. This study aims to clarify the potential of CDH3 as biomarker for TSCC. Here, meta-analysis, bioinformatics, along wet-lab techniques were employed to evaluate the diagnostic, as well as the prognostic value of CDH3 in diverse types of cancers, especially TSCC. Meta-analysis was used to determine the influence of CDH3 on prognostic and clinicopathological features in numerous cancers. Molecular biology function was used to investigate the role of CDH3 in TSCC cells. The relationship of CDH3 with tumor-infiltrating immune cells (TIICs) in TSCC was assessed using CIBERSORT. Moreover, gene set enrichment analysis (GSEA) was done based on TCGA. Besides, the hub genes and associated cascades were uncovered based on gene co-expression with CDH3. CDH3 upregulation correlated with worse overall survival and disease-free survival in various cancers. CDH3 was validated as an independent risk factor for HNSC and was linked to the onset of tumors, tumor stage, and infiltration depth. CDH3 silencing inhibited cell growth and induced apoptosis of the CAL-27 cell line. CDH3 expression level correlated with infiltration by macrophages, T cells, T cell regulatory cells (Tregs), and plasma cells in TSCC. GSEA revealed that CDH3 influences multiple cancer-associated cascades. Besides, CBX3, CCHCR1, along NFYC were identified as the core hub genes for CDH3. We identified CDH3 as a pan-cancer gene with potential prognostic and diagnostic significance in various cancers, particularly in TSCC, where it is tumorigenic.

Мікробіоценоз та стан місцевого мукозального імунітету ротової порожнини дітей і підлітків з хворобами печінки

The purpose of the study was to study the relationship between the state of the oral cavity microbiocenosis and the level of local immunity in children and adolescents with chronic liver diseases. Materials and methods. 45 children aged 10 to 16 years, who were treated in the public utility "City Children's Clinical Dental Hospital of the Poltava City Council" were examined. All children were divided into 2 groups: the main group – children and adolescents with chronic hepatitis (n = 26) with diseases of concomitant oral mucosa and periodontal disease; control group – children of the same age without concomitant somatic pathology (n = 20). In all observation groups, the state of oral hygiene was recorded using the simplified oral hygiene index (Green-Vermillion, 1964) and the intensity of the inflammatory process in the periodontal tissues, which was assessed by the papillary-marginal-alveolar index modified by Parma (1960). The degree of dysbiosis in the oral cavity was determined using the enzymatic method of A. P. Levitsky by the ratio of the relative activity of urease and lysozyme. The state of local immunity was investigated by the level of immunoglobulins IgA, IgM, IgG and secretory immunoglobulin sIgA. Results and discussion. It was found that the majority of patients with chronic hepatitis had an unsatisfactory and even poor state of oral hygiene, according to the Green-Vermillion simplified oral hygiene index, in combination with moderate and severe gingivitis (according to the papillary-marginal-alveolar index). The most negative results were registered in children 9-13 years old. The effect of the low level of oral hygiene in children and adolescents with chronic liver diseases, which is accompanied by increased dysbiosis, was studied, which indicates a drop in the level of antimicrobial protection, suppression of local mucosal immunity, a decrease in lysozyme activity and a decrease in the content of secretory sIgA in the oral fluid. The mediated mechanism of sIgA action through the phagocyte activation system with subsequent lysis of pathogenic microorganisms is considered. Conclusion. Chronic liver diseases reliably lead to changes in the body's immunobiological reactivity, and also cause suppression of the protective mechanisms of the oral cavity and its local immunity, characterized by a decrease in the activity of lysozyme and secretory IgA in the oral fluid of sick children and adolescents

Prognostic value of the density of tumor-infiltrating lymphocytes in colorectal cancer liver metastases.

Tumor-infiltrating lymphocytes (TILs) have been reported to reflect the anti-tumor immune status of patients and to be correlated with their prognosis and therapeutic outcomes. However, the characteristics of the local immune status in metastatic tumors is poorly understood, as primary tumors have been the focus in most previous studies. In addition, the local immune status may be influenced by preoperative chemotherapy. The present study aimed therefore to investigate the relationship between the degree of TIL infiltration and the prognosis in patients with curative resection of colorectal cancer liver metastases and to examine the effects of preoperative chemotherapy on the function of immune cells. A total of 108 patients who underwent curative resection of colorectal cancer liver metastases in our department between May 1996 and January 2017 were enrolled in the present study. Peripheral blood samples were obtained within two weeks before surgery. TIL infiltration was evaluated by immunohistochemical staining of surgically resected specimens of liver metastases using anti-CD8/CD3 antibodies. The mean number of TILs in five different fields was calculated, and patients were classified into a high-TIL group and a low-TIL group. Furthermore, patients were divided into three groups as follows: i) A group of patients who did not receive preoperative chemotherapy; ii) a group of patients who received short-term preoperative chemotherapy for <6 months; and iii) a group of patients who received long-term preoperative chemotherapy for ≥6 months. The results demonstrated that the density of TILs in colorectal liver metastases was not correlated with the absolute peripheral lymphocyte count in all patients. Furthermore, the degree of CD8+TIL infiltration in liver metastases was significantly lower in the recurrence group compared with the recurrence-free group following hepatectomy. In all patients with colorectal liver metastases, the degree of CD8+TIL infiltration was significantly associated with the relapse-free and overall survival. In patients without preoperative chemotherapy, the degree of CD8+TIL infiltration was significantly associated with the relapse-free survival, and a high CD8+TIL presence tended to have a better effect on the overall survival than a low CD8+TIL presence. In the short-term chemotherapy group, the degree of CD8+TIL infiltration was significantly associated with the relapse-free and overall survival. In the long-term chemotherapy group, there were no significant differences between the high- and low- CD8+TIL groups in the relapse-free and overall survival. In contrast to CD8+TILs, CD3+TILs showed a poor prognostic ability. In summary, the degree of CD8+TIL infiltration in colorectal cancer liver metastases may be correlated with patient prognosis. However, in patients who received long-term chemotherapy before surgery, the degree of TIL infiltration was not necessarily associated with prognosis as the anti-tumor effects of TILs may decrease. The degree of CD8+TIL infiltration may therefore be considered as a useful prognostic factor in patients with colorectal liver metastases, but the prognostic accuracy may decrease in patients who received long-term chemotherapy.

RELATIONSHIP OF LYMPHOCYTE SUBPOPULATIONS IN BREAST CANCER PATIENTS WITH TREATMENT RESULTS

Introduction. Breast cancer (BC) is an immunogenic tumor. Immune cells infiltration of tumor tissue can affect the clinical course of the disease. The immunogenicity of breast cancer varies depending on the molecular subtype.The aim of this work was to study the main indicators of systemic and local immunity before patient’s treatment and to determine their relationship with the immediate neoadjuvant chemotherapy results.Materials and methods. Patients with stage II–III BC received standard neoadjuvant chemotherapy in accordance with the molecular subtypes. The percentage of the main effector and regulatory lymphocytes populations of systemic and local immunity was determined by flow cytometry.Results. A decrease in the level of effector CD8 and CD4 lymphocyte populations and an increase in the level suppressor populations in tumor tissue in comparison with peripheral blood indicate an immunosuppressive state of local immunity in BC patients. In tumor tissue, a high level of CD8+ PD-1+ and CD4+ PD-1+ cells were associated with a high level of regulatory CD4+ CD25highCD127–/low and CD8+ CD11b– CD28– lymphocytes. Differences were found in the significance of individual lymphocyte populations for the immediate results of treatment between patients with different subtypes of breast cancer.Conclusion. Determination of lymphocyte subpopulations correlating with the level of PD-1 cells, and the results of treatment in patients with different molecular BC subtypes, will help a clearer understanding of the antitumor immune response in this pathology, and will also serve as a basis for identifying immune biomarkers that can be used as additional predictive factors in various treatment options for BC patients.

A Radiomic Approach to Access Tumor Immune Status by CD8+TRMs on Surgically Resected Non-Small-Cell Lung Cancer

PurposeImmunotherapy has made breakthroughs in the treatment of non-small-cell lung cancer (NSCLC); however, only a subset of patients achieved long-term survival, so it is of great importance to find a biomarker of lung cancer thus guide immunotherapy. Studies have shown that the infiltration level of tissue resident memory CD8+ T cells (CD8+ TRMs) is positively correlated with lung cancer prognosis and can be an ideal biomarker for assessing the tumor local immune status. We screened the radiomic features associated with CD8+ TRMs as targets in NSCLC surgical specimens by radiomic approaches, and established a radiomic predictive model to assess the local immune status, which may provide a scientific reference for lung cancer treatment strategies.Patients and MethodsWe retrospectively analyzed the NSCLC surgical specimens immune cell database and extracted CD8+ TRMs cell data, preoperative CT scan data were achieved. A total of 97 patients containing complete preoperative data were included, radiomic features were extracted from the preoperative CT image data. All the patients were divided into two groups, namely high-CD8+ TRMs infiltrated group and low-CD8+ TRMs infiltrated group, based on the proportion of CD8+ TRMs cells subset in the immune cell population. The most valuable radiomic features and semantic features were extracted and selected, and a neural network model was established to predict the level of CD8+ TRMs cell infiltration level to assess the tumor local immune status.ResultsThe NSCLC tumor immune status predictive model was built to discriminate high- from low-CD8+ TRMs with an area under the curve (AUC) of 0.788 (95% CI) in the training set and 0.753 (95% CI) in the validation set.ConclusionThe radiomic models using CT image data showed a good predictive performance for accessing NSCLC immune status thus has great potential for personalized therapeutic decision making.

37P Interleukin-1β effect on the efficacy of cytostatic drugs in vitro

Interleukin-1β (IL-1β) is an inflammatory cytokine; however, in the tumor microenvironment it exhibits pro-oncogenic properties, inducing angiogenesis, metastasis, and local immunosuppression. In this regard, various approaches to the use of IL-1β inhibitors in cancer patients are being considered. However, such treatment should be based on knowledge of cytokine expression in tumor tissue and local immune status.

Possible Immunotherapeutic Strategies Based on Carcinogen-Dependent Subgroup Classification for Oral Cancer.

The oral cavity serves as an open local organ of the human body, exposed to multiple external factors from the outside environment. Coincidentally, initiation and development of oral cancer are attributed to many external factors, such as smoking and drinking, to a great extent. This phenomenon was partly explained by the genetic abnormalities traditionally induced by carcinogens. However, more and more attention has been attracted to the influence of carcinogens on the local immune status. On the other hand, immune heterogeneity of cancer patients is a huge obstacle for enhancing the clinical efficacy of tumor immunotherapy. Thus, in this review, we try to summarize the current opinions about variant genetic changes and multiple immune alterations induced by different oral cancer carcinogens and discuss the prospects of targeted immunotherapeutic strategies based on specific immune abnormalities caused by different carcinogens, as a predictive way to improve clinical outcomes of immunotherapy-treated oral cancer patients.

ВЛИЯНИЕ КОМПЛЕКСНОГО ЛЕЧЕНИЯ ГИНГИВИТА С ПРИМЕНЕНИЕМ ЖЕВАТЕЛЬНОГО ФИТОСУБСТРАТА У ЖЕНЩИН С ОТЕКАМИ, ВЫЗВАННЫМИ БЕРЕМЕННОСТЬЮ, НА СОДЕРЖАНИЕ ПРОВОСПАЛИТЕЛЬНЫХ ЦИТОКИНОВ В РОТОВОЙ ЖИДКОСТИ

Introduction. Edema of pregnant women is a pathological condition in the second half of pregnancy, in which disorders of the functions of vital organs are noted and an exacerbation of chronic and sluggish inflammatory diseases occurs. Inflammatory periodontal disease and dental caries increase especially in the third trimester, and are most pronounced in complicated pregnancies. Changes in the cytokine profile in the mixed saliva of pregnant women reflect the state of local immunity and tissues of the oral cavity and indicate the participation of immunocompetent cells of the placenta and fetus in the response to the inflammatory process. Purpose: to characterize the effect of complex treatment of gingivitis with the use of a chewing phytosubstrate in women with edema caused by pregnancy on the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) in the oral fluid. Materials and methods: the level of cytokines IL-1β, IL-6, TNF-α in the oral fluid was determined before and after complex treatment of gingivitis with the inclusion of a chewing phytosubstrate in women with edema caused by pregnancy. Conclusion: Inclusion in the complex treatment of gingivitis in women with edema caused by pregnancy, a chewable phytosubstrate containing 0.1 g of dry matter extract (oak bark, alder stems, birch buds, chamomile flowers, thyme grass) and 1.0 g beeswax, has a pronounced therapeutic effect, reducing the content of pro-inflammatory cytokines in the oral fluid, which reflects the suppression of the inflammatory process.

Environmentally enriched housing conditions affect pig welfare, immune system and gut microbiota in early life

BackgroundConventional pig housing and management conditions are associated with gastrointestinal pathophysiology and disease susceptibility in early life. Developing new strategies to reduce both therapeutic and prophylactic antibiotic use is urgent for the sustainable swine production globally. To this end, housing methodology providing effective environmental enrichment could be a promising alternative approach to reduce antibiotic usage, as it has been proven to positively influence pig welfare and immune status and reduce susceptibility to infections. It is, however, poorly understood how this enriched housing affects systemic and local pulmonary immune status and gut microbiota colonization during early life. In the present study, we compared the effects of two housing conditions, i.e., conventional housing: (CH) versus enriched housing (EH), on immune status and gut microbiota from birth until 61 days of age.ResultsThe expected benefits of enrichment on pig welfare were confirmed as EH pigs showed more positive behaviour, less aggression behaviour during the weaning transition and better human animal relation during the post weaning phase. Regarding the pigs’ immune status, EH pigs had higher values of haemoglobin and mean corpuscular volume in haematological profiles and higher percentages of T cells and cytotoxic T cells in peripheral blood. Furthermore, EH pigs showed higher ex vivo secretion of IL1ß and TNF-α after lipopolysaccharide stimulation of whole blood than CH pigs. The structure of the developing faecal microbiota of CH and EH pigs significantly differed as early as day 12 with an increase in the relative abundance of several bacterial groups known to be involved in the production of short chain fatty acids, such as Prevotella_2, Christensenellaceae_R_7_group and Ruminococcus gauvreauii group. Furthermore, the main difference between both housing conditions post weaning was that on day 61, CH pigs had significantly larger inter-individual variation of ileal and colonic microbiota than EH pigs. In addition to housing, other intrinsic factors (e.g., sex) were associated with gut microbiota development and immune competence.ConclusionsIn addition to the known welfare benefits for pigs, environmentally enriched housing also positively drives important aspects of the development of the immune system and the establishment of gut microbiota in early life. Consequently, EH may contribute to increasing productivity of pigs and reducing antibiotic use.

Peculiarities of genital tract microbiocenosis and immunological homeostasis in reproductive-age women with uterine leiomyoma

The objective: To determine the features of the microbiocenosis of the genital tract and immunological homeostasis and in women of reproductive age with uterine leiomyoma.Materials and methods. The microbiocenosis of the genital tract and immunological homeostasis of 308 women with uterine leiomyoma aged 23–49 years were studied. The control group included 30 healthy women aged 24–37 years. Results. In women of reproductive age, the development of uterine leiomyoma is associated with a significant violation of the microecology of the genitals, the presence of nonspecific vaginitis and bacterial vaginosis, increased frequency and concentration of pathogenic flora (staphylococci and streptococci with hemolytic properties, enterobacteria), STIs or reducing the concentration of protective microflora.The study of the peculiarities of the functioning of the immune system at the local level in the presence of uterine leiomyoma indicates unidirectional disorders in the state of local immunity and changes in the protective function of cervical mucus in the examined women. Thus, under conditions of uterine leiomyoma, there is a significant activation of local immunological factors, as evidenced by a significant increase in the concentration of IgG, IgA and the appearance of IgM in cervical mucus in 27,5–32,5 % of women with uterine leiomyoma. In addition, there was suppression of phagocytic activity of neutrophils, which was manifested by a significant decrease in activity and intensity of phagocytosis, with a decrease in their functional reserve by NRT test, which creates conditions for intracellular persistence of infection, activation and persistence of inflammatory progression.Conclusions. The obtained data indicate a violation of the microecology of the genitals and the intensity of immunogenesis in women with uterine leiomyoma, which indicates that the inflammatory process of the genitals is one of the significant factors that lead to the emergence and progression of uterine leiomyoma.

ERBB1/2/3 Expression, Prognosis, and Immune Infiltration in Cutaneous Melanoma.

BackgroundThe four ERBB tyrosine kinase family members [ERBB1 (epidermal growth factor receptor, EGFR), ERBB2 (HER2), ERBB3 (HER3), and ERBB4 (HER4)] (ERBB receptor family) have been shown, according to previous studies, to be related to the cutaneous melanoma. ERBB3 is the only member of the ERBBs that lacks tyrosine kinase activity and thus needs to dimer with other tyrosine kinases receptors to trigger the signaling pathway, while ERBB3 may dimer with all members of the ERBB family. Melanoma progression depends on activation of ERBB signaling, especially the ERBB3/ERBB2 cascade. There are lymphocytes and T cell infiltrates in melanoma. Numerous pieces of evidences indicate that local immune status plays an important role in the formation of anti-tumor immune responses. However, the relationship between the ERBBs and prognosis and immune infiltration in cutaneous melanoma is not completely clear.MethodsThe expression of the ERBBs was analyzed through the Oncomine database, Gene Expression Profiling Interactive Analysis (GEPIA), respectively. Immunohistochemistry of ERBBs was obtained from the Human Protein Atlas is increased before HPA database. ERBBs genes expression and mutation analysis in cutaneous melanoma from the cBioPortal. Functional annotation and Kyoto Encyclopedia of Genes and Genomes is increased before KEGG pathway enrichment analysis from the Metascape. Correlations between ERBBs and 31 genes that were close to each other and frequently altered were explored by GEPIA. Using the GEPIA database, we also investigated the relationship between ERBBs and myeloid-derived suppressor cells (MDSC) in cutaneous melanoma. The disease-free survival and different tumor stages of ERBBs were evaluated by GEPIA. The correlation of ERBBs and tumor-infiltrating immune cells and prognostic(5 years survival rates) was tested by the Tumor Immune Estimation Resource (TIMER).ResultsIn general, the expression levels of ERBB1/2 in cutaneous melanoma were lower than those in normal skin tissue. By contrast, the ERBB3 expression level was higher in cutaneous melanoma than in normal skin tissue. Low expression of ERBB1/2 and high expression of ERBB3 were detrimental to the 5 years survival of cutaneous melanoma patients (ERBB1: log-rank P: 0.03; ERBB2: log-rank P: 0.008; ERBB3: log-rank P: 0.039). ERBB4 expression may not affect the prognosis of patients with cutaneous melanoma. ERBBs may not play a role in the tumor stage and disease-free survival in cutaneous melanoma patients. The relationship between the ERBB family and 31 genes that were close to each other and frequently altered is demonstrated as the genes regulated by the ERBB family being mainly concentrated in the RAS/RAF/MEK/ERK signaling pathway. ERBB2 can induce infiltration of CD8+ T cells and B cells, while ERBB3 can induce infiltration of CD4+ T cells, CD8+ T cells, and Neutrophil cells. ERBBs are more significantly associated with M1 macrophages, dendritic cells, Th1, Th2, Th17, and Treg cellular immune markers (Cor > 0.2). ERBB2/3 were related to MDSC in cutaneous melanoma, including human mononuclear myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC), and may influence the progression of cutaneous melanoma through MDSC, but the conclusion needs further probing.ConclusionThis study investigated the prognosis and immune infiltration of the ERBB family in cutaneous melanoma. Our results suggest that ERBB1/2/3 may serve as early prognostic markers and potential therapeutic targets in cutaneous melanoma.

Порушення місцевого імунітету ротової порожнини у працівників агропромислових виробництв з генералізованим пародонтитом за впливу пестицидів

Among dental diseases, periodontal diseases occupy a prominent place. The polyetiology and polypathogenicity of periodontal diseases are different in nature: pathological processes at the level of the whole organism, its cells and environments, periodontal tissues, biochemically reactive substrates. The significant impact of adverse environmental factors on the state of human organs and systems is confirmed by the tendency to increase the incidence of periodontal disease in industrialized countries, which in different age groups ranges from 80% to 100%. Pesticides are one of the most important factors determining the well-being and balance of the human-environment system today. This is due to their characteristics as chemical pollutants, which deliberately and purposefully contributes to the environment pollution. The main among these features are constant and excessive scattering over large areas; high biological activity on pets, as well as on humans and other living organisms; the ability to persist in the environment and circulate in its objects; metabolized in biological objects and transformed into the environment with the formation of more toxic and dangerous, compared to the original, compounds; the ability to cause the development of long-term effects. The group of risk of periodontal tissue diseases naturally includes employees of agricultural enterprises, who in the process of work are exposed to occupational pathogens of different nature, intensity and duration of action. Continuous intake of agro-industrial xenobiotics creates a chemical load, causes the occurrence of toxic hypoxia, anemia, imbalance in the immune system, promotes the activation of endogenous intoxication, which in turn is projected on the periodontal tissues, and disease of tooth-retaining tissues. The purpose of our research was to study the state of local immunity of the oral cavity in agro-industrial workers with generalized periodontitis under the influence of pesticides. Material and methods. To determine the changes in local immunity in the oral and gingival fluid we determined the concentrations of lysozyme, sIgA, IgA and IgG in 39 patients with generalized periodontitis who were not adversely affected by greenhouse factors (comparative group) and 81 agricultural workers (41 people in open (I main group) and 40 people in closed soils) II main group), exposed to pesticides). The obtained values were compared with data in 31 dentistically healthy people not in contact with pesticides (control group). Results and discussion. The obtained results showed that generalized periodontitis marked changes in the local immune mechanisms of the oral cavity. However, the most pronounced violations were observed in patients with generalized periodontitis working in closed and open soils under the influence of pesticides, and in subjects who were exposed to toxic effects of chemicals in closed soil, this trend was more intense. Conclusion. The study results proved that agro-industrial workers in contact with pesticides in open and closed soils have significant disturbances in the local immune system, which was characterized by a decrease in the levels of immunoglobulins A, G, sIgA and lysozyme in oral and gingival fluids

Integral assessment of markers of the local infectious and inflammatory process in women with preterm birth in multiple pregnancies

Hypothesis/Aims of study. Premature birth in multiple pregnancies remains an important object of research, since it is the main factor in poor perinatal outcomes, and their heterogeneous mechanisms determine the ineffectiveness of prediction and prevention methods. In the pathogenesis of premature birth, as is known, one of the leading links is inflammation caused by infections of the lower genital tract (40%). In multiple pregnancies, which in most cases occur as a result of assisted reproductive technology treatment (70%) and are mainly accompanied by complications, pregravid preparation and antenatal observation include more careful control and correction of local infectious and inflammatory processes. In this regard, the persisting high rate of premature birth in multiple pregnancies (about 54%) demonstrates the ambiguity of the opinion about the suppressive role of the infectious factor in the induction of premature birth and determines the need for studying its contribution to multifactorial genesis. The aim of this study was to conduct an integral assessment of markers of the local infectious and inflammatory process in women with PB in multiple pregnancies.&#x0D; Study design, materials and methods. We performed a comprehensive study of the bacteriological composition of the lower genital tract discharge using microscopic, bacteriological, and molecular biological methods (Femoflor 16 test) and assessed the local inflammatory status (ImmunoQuantex test) in 30 pregnant women with dichorionic diamniotic twins. The main group consisted of women with premature birth (n = 13), the control group comprising those with term birth (n = 16), while patients with induced premature birth (n = 2) were not included in the comparative analysis.&#x0D; Results. This study was the first to determine the features of vaginal microbiocenosis and the local immune status in women with premature birth in multiple pregnancies. In general, the study cohort had a low inflammatory status and normal or intermediate types of vaginal biotope. The most common disruptions (24.1%) were vaginal dysbiosis, expressed in a small amount of Lactobacillius spp., and non-specific vaginitis associated with Mycoplasma hominis. The local immune status of women with premature birth was characterized by a relative decrease in the mRNA expression of such innate immunity genes as IL1B, TNF, TLR4, and GATA3. An integrated assessment of the studied parameters based on the data obtained allowed us to build a mathematical model for predicting premature birth with the probability of 87.6%.&#x0D; Conclusion. The integral assessment of infectious and inflammatory markers is important from the standpoint of not only their possible identification as predictors, but also a general understanding of the genesis of premature birth.

Nocardia Rubra Cell Wall Skeleton Up-Regulates T Cell Subsets and Inhibits PD-1/PD-L1 Pathway to Promote Local Immune Status of Patients With High-Risk Human Papillomavirus Infection and Cervical Intraepithelial Neoplasia.

The Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immune enhancer, which has been widely used in human cervix diseases such as cervical erosion, but the mechanism of Nr-CWS enhancing immunity is still unclear. The purpose of this study was to explore the effect and mechanism of Nr-CWS on the local immune status of cervical tissue in patients with high-risk human papillomavirus (HR-HPV) infection and cervical precancerous lesion, cervical intraepithelial neoplasia (CIN). The recruited patients with HR-HPV infection and CIN were treated with Nr-CWS. The specimens were taken from these patients before and after local application of Nr-CWS respectively. The normal control specimens were tested simultaneously. Serial section analysis of immunohistochemistry and co-expression analysis were performed to characterize populations of T cells and the expressions of programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1). The levels of cytokines in local cervical tissue were also detected. Nr-CWS significantly increased T cells including CD4+, CD8+ T cells, and reduced the expression of PD-L1 in the patients’ local cervical tissues. Co-expression analyses showed that the proportions of PD-1+CD4+ cells in CD4+ T cells and PD-1+CD8+ cells in CD8+ T cells decreased after Nr-CWS application. Furthermore, the increase in the number of immune cells was accompanied by increased pro-inflammatory cytokines interleukin-12 (IL-12), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and decreased suppressive cytokine IL-10. The results indicate that Nr-CWS, as an immunotherapeutic agent for HR-HPV infection and CIN, plays an immune promoting role related to the upregulation of T cell subsets and the inhibition of PD-1/PD-L1 pathway.

Immunodiagnostics, immunotherapy and immunoprophylaxis in the clinic of otolaryngology. Message 2. Indicators of local immunity in assessment of clinical and laboratory status of patients in inflammatory ENT diseases (Analytical summary)

Topicality: It is considered proven that the state of the immune system determines the development and course of many pathological processes, which are based on inflammation. At the same time, taking into account modern trends in assessing the immunological status, a mandatory component is to determine the state of local immunity in the upper respiratory tract. Aim: to conduct an integral analysis of data to determine the state of local immunity in inflammatory diseases of the upper respiratory tract (URT) to select the optimal necessary informative indicators. Materials and methods: A generalization of the data of immunological studies of 168 people with inflammatory pathology of the upper respiratory tract (VDS) was carried out, of whom 42 had chronic tonsillitis (CT), 36 – chronic rhinitis (HR – catarrhal form), 40 – chronic pharyngitis (CP), 28 – secretory mean otitis media (CO), 22 people made up the control group (C) of practically healthy donors. The age of the surveyed was from 14 to 60 years, the duration of the diseases was from 1 to 5 years, female patients predominated (~ 60%). The examination was carried out at the stage of clinical remission. The material for the research was mixed saliva, in which the content of immunolobulins and citrokines was investigated by the ELISA method: enzyme immunoassay, the following factors of immunity and inflammation in the CGS were determined: - secretory and monomeric form of immunoglobulin A (Hema Medica, RF); - immunoglobulins of classes G, M (Hema Medica, RF); - interleukins – 1β; 4; 8; 10 (Cytokine, RF); - interferons α and γ (Cytokine, RF); - pro- and defensins (Nucalt bioteknology, Netherlands); - macrophage inflammatory protein-Mip-1b (Assauro, USA); - salivary lysozyme (Diagnostik Nord, Germany). Statistical processing was carried out using the methods of Student’s t-criterion and angular transformation “φ” according to Fisher. Results: Integral of all methods for determining various types of immunity in diseases of the upper respiratory tract with a chronic course is the insufficiency of factors of both innate and acquired immunity, especially during the period of clinical remission of the disease. A special role in protective reactions belongs to the humoral component, in which the most stable indicator is the level of class A secretory immunoglobulin; it has been shown that almost all the studied components of the immune response had abnormalities in the presence of a chronic inflammatory process in the upper respiratory tract and they can be presented as a line the degree of decrease in the frequency of deviations: secretory IgA, IgG., pro-inflammatory cytokines (IL1β and IL-8), γ-interferon, lysozyme, defensin-β, Mip-1b. Conclusion: The developed criteria and approaches to assessing systemic immunity in patients with inflammatory diseases of the upper respiratory tract can be used in examining patients and assessing the effectiveness of therapy.

Эффективность коррекции цитокинового компонента локального иммунитета в лечении рецидивирующего бактериального вагиноза, ассоциированного с герпетической инфекцией

The risk of bacterial vaginosis (BV) and recurrence rate increase in the presence of herpesviruses, which is associated with changes in local immune response. Objective. To determine the effect of exogenous cytokines on the cytokine component in local immunity and its efficacy in the treatment of recurrent bacterial vaginosis (RBV) associated with herpesvirus infection. Patients and methods. Eighty women of reproductive age with RBV and herpesvirus infection were randomized into two groups: group I (n = 40) received Clindamycin and a complex of exogenous cytokines (Superlymph®), group II – Clindamycin and placebo. The biocenosis and cytokine levels in vaginal discharge were examined. Results. Recovery occurred in 95% (38/40) of patients in group I versus 77.5% (31/40) of those using placebo; p = 0.05, OR = 5.52 (95% CI: 1.11–27.43). The recurrence rate for 12 months was 12.6% (5/40) versus 33.5% (13/40), respectively, p = 0.01, with a 3-fold decrease in the risk of recurrence (OR = 0.30; 95% CI: 0.09–0.93). There was the restoration of vaginal biocenosis and the decrease in viral release and pro-inflammatory cytokine levels by an average of 1.5 times (p &lt; 0.001) compared with baseline values in patients who received Superlymph®. Conclusion. The complex of exogenous cytokines contributes to the normalization of cytokine component in local immune status and vaginal microbiota and to the decrease in recurrence rate of BV associated with herpesvirus infection. Key words: herpes infection, immunomodulatory therapy, recurrent bacterial vaginosis, Superlymph, cytokines