Number Of Peripheral Blood Lymphocytes Research Articles

Clinicopathological and genetic analysis of interstitial disease-like pulmonary intravascular large B cell lymphoma

Objective: To investigate the clinicopathological features and genetic mutation status of pulmonary intravascular large B cell lymphoma. Methods: The clinicopathological data of eight patients diagnosed with pulmonary intravascular large B cell lymphoma, from April 2018 to May 2023, were retrospectively analyzed. The genetic profile of six patients was detected via next-generation sequencing (NGS) and followed up. Results: All patients included one male and seven females, with a median age of 64 years (ranging from 45 to 66 years). Respiratory symptoms were the most common (7 cases), B symptoms in two cases, hemophagocytic syndrome in two cases. Multiple diffuse ground-glass opacities in both lungs were observed based on the high-resolution chest CT scan. Six cases of mild to moderate ventilation or diffusion dysfunction were observed based on the pulmonary function tests. Moreover, two cases of hypoxemia and two cases with type Ⅰ respiratory failure were recorded. The serum lactate dehydrogenase level increased (7/8), β2-MG level increased (2/8), neuron-specific enolase level increased (7/8), total number of peripheral blood lymphocytes decreased (7/8), and clinical stages were all stage Ⅳ. The neoplastic lymphoid cells were lodged in the lumina of venules and capillaries of the alveolar septum; the tumor cells were large, with prominent nucleoli and frequent mitotic figures. The malignant cells were detected in the extravascular surrounding lung tissue in all cases. The tumor cells expressed mature B cell-associated antigens CD20 and CD79a, and the vascular endothelial markers CD31 and CD34 showed that the tumor cells were filled in the blood vessels, infiltrated blood vessel walls, and perivascular areas. One case was germinal center-type, seven cases were non-germinal center-type, two cases were double-expressing lymphoma, and all cases were EBER-negative. Furthermore, the top five genes with mutation frequencies detected by NGS were MYD88 (5/6), PIM1 (5/6), CD79B (4/6), TCF3 (4/6), and TP53 (3/6). Of the eight cases, seven patients received R-CHOP-based chemotherapy, six cases had complete remission after chemotherapy, one case died, and one case was lost to follow-up. Conclusions: Pulmonary vascular large B cell lymphoma is rare, which shares similar patterns with interstitial lung disease on imaging. Transbronchial lung biopsy is an effective method to confirm the diagnosis. Immunochemotherapy with BTK inhibitors can provide a survival advantage for patients in the future based on molecular typing.

Expression of γδ T cells and lymphocyte subsets in newly diagnosed multiple myeloma patients

ObjectiveTo retrospectively analyze the expression and significance of γδ T cells and lymphocyte subsets in peripheral blood on patients with multiple myeloma (MM). MethodsFifty-five patients with multiple myeloma admitted to Yangpu Hospital Affiliated to Tongji University from January 2022 to August 2023 were selected as the disease group, and were categorized into stage I group, stage II group and stage III group according to the International Staging System (ISS) of multiple myeloma. All included patients were consecutive visits. Another 30 cases of healthy people with physical examination were selected as the control group. Flow cytometry was used to detect the γδ T cells and lymphocyte subsets in the peripheral blood of the subjects. After clinical indicators of patients and healthy controls were collected, the statistical analysis was conducted. ResultsCompared with the control group, the percentage of γδ T cells and CD8+ T cells in the disease group were higher, while, the absolute numbers of total peripheral blood lymphocytes (LYMT) and CD19+ B cells, percentage of CD19+ B cells, CD3+ T cells, CD4+ T cells were lower (P​<​0.05). The percentage of γδ T cells (P​<​0.001), the percentage of CD19+ B cells (P​=​0.003), the absolute number of CD3+ T cells (P​=​0.010), the absolute number of CD8+ T cells (P​=​0.002) were the significant influential factors of MM. γδ T cells (P​=​0.004), neutrophils (P​<​0.001), neutrophil to lymphocyte ratio (P​=​0.003), and white blood cell count (P​<​0.001) were statistically different in different stages. ROC curve suggested that the area under the curve of the percentage of γδ T cells in predicting the MM were 0.973 (P​<​0.001) which had certain diagnostic value. Conclusionsγδ T cells and lymphocyte subsets (CD8+ T cells, CD19+ B cells, CD3+ T cells, etc.) in patients with newly diagnosis of MM can reflect the immune function of the patient’s organism, which is a key factor of MM. γδ T cells influence the staging of MM patients, and also have certain diagnostic value.

GENETIC ABLATION OF THE C-TYPE LECTIN RECEPTOR CLEC2D INCREASES PERITONITIS MORTALITY, INFLAMMATION, AND PHYSIOLOGY WITHOUT DIMINISHING ORGAN INJURY.

Background: Sepsis accounts for substantial morbidity and mortality motivating investigators to continue the search for pathways and molecules driving the pathogenesis of the disease. The current study examined if the novel C-type lectin receptor (CLR), Clec2d, plays a significant role in the pathogenesis of sepsis. Methods: Clec2d knockout (KO) mice were fully backcrossed onto the C57/BL6 background. Acute endotoxemia was induced with an intraperitoneal injection of lipopolysaccharide (LPS). Sepsis was induced in two different models, cecal ligation and puncture (CLP) and Pseudomonas aeruginosa pneumonia. Both models were treated with antibiotics and fluid resuscitation. In the sepsis models, physiologic and hematologic measurements were measured at 24 h by collecting a small sample of peripheral blood. Mortality was followed for 14 days. Results : A total of 197 mice were studied, 58 wild type (WT) and 54 knock-out (KO) in the LPS model; 27 wild type and 21 KO mice in the CLP model; and 22 WT and 15 KO mice in the pneumonia model. Clec2d KO mice had greater mortality in the LPS and CLP studies but not the pneumonia model. There were significant differences in multiple parameters determined 24 h post sepsis between mice who subsequently died and those lived. Consistent with previous reports in the CLP model, higher concentrations of IL-6, increased numbers of peripheral blood lymphocytes and greater renal injury were found in the dying mice. In contrast, in the pneumonia model, IL-6 was higher in the surviving mice; however, the IL-6 levels in the pneumonia model (0.6 ± 0.3 ng/mL mean ± SEM) were less than 2% of the IL-6 levels of mice that died in the CLP model (41 ± 9 ng/mL, mean ± SEM). There were no differences in the lymphocyte count or renal injury between living and dying mice in the pneumonia model. In both sepsis models, dying mice had lower heart rates, respiratory rates, and body temperatures. These values were also lower in the KO mice compared to the WT in CLP, but the breath rate and body temperature were increased in the KO pneumonia mice. Conclusion: The C-type lectin receptor Clec2d plays a complicated role in the pathogenesis of sepsis, which varies with source of infection as demonstrated in the models used to study the disease. These data highlight the heterogeneity of the responses to sepsis and provide further evidence that a single common pathway driving sepsis organ injury and death likely does not exist.

Immunotoxicity of 2-Acetyl-4-tetrahydroxybutylimidazole in BALB/c mice with different vitamin B6 nutritional statuses

Caramel color is a widely used food pigment, and 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a by-products of Class III caramel color. Some studies have shown that THI can reduce the number of peripheral blood lymphocytes. However, the comprehensive mechanism of THI immunotoxicity requires further study. In this study, the effects of THI on lymphocyte count, humoral immunity, cellular immunity and nonspecific immunity were determined and the effect of the nutritional status of VB6 on THI immunotoxicity was evaluated. Female BALB/c mice were divided into 3 groups and fed chow containing different doses of VB6: VB6-normal (6 mg/kg VB6), VB6-deprived (0.5 mg/kg VB6) or VB6-enhanced (12 mg/kg VB6) feed. Each group was further divided into 4 subgroups and treated with THI (0.5, 2.5 or 12.5 mg/kg bw) or the solvent control by gavage for 30 days. The thymic cortical thickness was measured with ViewPoint; the proportions of major immune cells and T cells in peripheral blood and tissues were detected via flow cytometry; the transformation and proliferation abilities of T and B cells were detected via T and B lymphocyte proliferation assays; NK cell activity was assessed via lactate dehydrogenase assays; humoral immune function was assessed via plaque-forming cell assays; and the immune function of T lymphocytes was assessed via delayed type hypersensitivity assays. The results showed that compared with those in the corresponding control group, the white blood cell count and lymphocyte count decreased significantly in all the VB6-deprived groups, in the 2.5 and 12.5 mg/kg VB6 groups, and in the 12.5 mg/kg VB6-enhanced group. With increasing THI dose, the thymic cortical layer became thinner. In the thymus, THI increased the proportions of CD3+ T cells and mature CD8+ T cells and decreased the proportions of immature double-positive, double-negative T cells and CD69-expressing lymphocytes. The proportions of naïve T cells and Tcm (central memory T) cells related to homing decreased. The proportion of mature T cells in the spleen decreased significantly. The proliferation of T cells stimulated by ConA decreased after THI exposure. VB6-deficient mice were more sensitive to THI immunotoxicity, and supplementation with VB6 had a certain protective effect on these mice. The results of the PFC and NK cell activity assays indicated that THI exposure might not affect humoral immune or innate immune function.

Add-on sirolimus for the treatment of mild or moderate systemic lupus erythematosus via T lymphocyte subsets balance

ObjectiveThe efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore,...

Nivolumab receptor occupancy on effector regulatory T cells predicts clinical benefit.

Immune checkpoint inhibitor discovery represents a turning point in cancer treatment. However, the response rates of solid tumors remain ~10%-30%; consequently, prognostic and immune-related adverse event (irAE) predictors are being explored. The programmed cell death protein 1 (PD-1) receptor occupancy (RO) of PD-1 inhibitors depends on the number of peripheral blood lymphocytes and their PD-1 expression levels, suggesting that the RO may be related to efficacy and adverse events. As PD-1 inhibition affects each T-cell subset differently, the RO of each cell population must be characterized. However, relevant data have not been reported, and the prognostic relevance of this parameter is not known. In this study, we aimed to clarify the association between the nivolumab RO in each T-cell population and patient prognosis and reveal the development of irAEs in nivolumab-treated patients. Thirty-two patients were included in the study, and the mean follow-up period was 364 days. The nivolumab RO on effector regulatory T cells (eTregs) was significantly lower in the group that presented clinical benefits, and a significant negative association was observed between PD-1 occupancy on eTregs and all-cause mortality. The results suggest that the nivolumab RO on eTregs may be a prognostic factor in PD-1 inhibitor therapy, implying that the inhibition of PD-1/PD-ligand 1 (PD-L1) signaling on eTregs may attenuate antitumor effects.

Ex Vivo Production of IL-1β and IL-10 by Activated Blood Cells of Wistar Rats with Different Resistance to Hypoxia after Systemic Inflammatory Response Syndrome.

We studied spontaneous and ex vivo activated cytokine production by blood cells of male Wistar rats with different resistance to hypoxia against the background of an LPS-induced systemic inflammatory response. In rats with low (LR) and high resistance (HR) to hypoxia, the number of leukocytes, granulocytes, and peripheral blood lymphocytes was determined, the levels of spontaneous and stimulated production of IL-1β and IL-10 and their ratio were assessed ex vivo. Against the background of a systemic inflammatory response, only HR animals showed a decrease in spontaneous and stimulated production of IL-1β and spontaneous production of IL-10. The IL-1β/IL-10 ratio decreased only in LR rats during the development of a systemic inflammatory response, while in HR animals, no changes in this indicator were observed. The obtained data suggest a high proinflammatory potential of blood cells in LR rats, which apparently determines the development of a more severe course of the systemic inflammatory response.

Negative serum (1,3) -β-D-glucan has a low power to exclude Pneumocystis jirovecii pneumonia (PJP) in HIV-uninfected patients with positive qPCR

ObjectiveThe current study evaluated the diagnostic performance of serum (1,3)-beta-D Glucan (BDG) in differentiating PJP from P. jirovecii-colonization in HIV-uninfected patients with P. jirovecii PCR-positive results.MethodsThis was a single-center retrospective study between 2019 and 2021. The diagnosis of PJP was based on the following criteria: detection of P. jirovecii in sputum or BAL specimen by qPCR or microscopy; Meet at least two of the three criteria: (1) have respiratory symptoms of cough and/or dyspnea, hypoxia; (2) typical radiological picture findings; (3) receiving a complete PJP treatment. After exclusion, the participants were divided into derivation and validation cohorts. The derivation cohort defined the cut-off value of serum BDG. Then, it was verified using the validation cohort.ResultsTwo hundred and thirteen HIV-uninfected patients were enrolled, with 159 PJP and 54 P. jirovecii-colonized patients. BDG had outstanding specificity, LR, and PPV for PJP in both the derivation (90.00%, 8.900, and 96.43%) and the validation (91.67%, 9.176, and 96.30%) cohorts at ≥ 117.7 pg/mL. However, it had lower sensitivity and NPV in the derivation cohort (89.01% and 72.97%), which was even lower in the validation cohort (76.47% and 57.89%). Of note, BDG ≥ 117.7 pg/mL has insufficient diagnostic efficacy for PJP in patients with lung cancer, interstitial lung disease (ILD) and nephrotic syndrome. And although lymphocytes, B cells, and CD4+ T cells in PJP patients were significantly lower than those in P. jirovecii-colonized patients, the number and proportion of peripheral blood lymphocytes did not affect the diagnostic efficacy of serum BDG.ConclusionsSerum BDG ≥ 117.7 pg/mL could effectively distinguish P. jirovecii-colonization from infection in qPCR-positive HIV-uninfected patients with infectious diseases, solid tumors (excluding lung cancer), autoimmune or inflammatory disorders, and hematological malignancies. Of note, for patients with lung cancer, ILD, and nephrotic diseases, PJP should be cautiously excluded at BDG < 117.7 pg/mL.

Systemic Inflammatory Status of Patients with Obstructive Sleep Apnea Syndrome and the Predictive Value of Heparin-Binding Protein.

Objective: To investigate the alteration of the systemic inflammatory status of patients with obstructive sleep apnea syndrome (OSAS) and the predictive value of heparin-binding protein (HBP) for OSAS. Methods: Patients with OSAS who were hospitalized in our hospital from 2020 January to 2022 December and diagnosed by polysomnography (PSG) (OSAS group, n = 79) were retrospectively studied and their relevant examination findings and demographic characteristics were recorded. Sex- and age-matched non-OSAS patients hospitalized at the same time were selected as the control group (control group, n = 28). Differences in peripheral blood neutrophil counts, lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), procalcitonin (PCT), and HBP were compared between the 2 groups. The predictive value of these markers for OSAS was analyzed using the receiver operating characteristic curve, and independent risk factors for OSAS were determined using logistic regression analysis. Peripheral blood was drawn from all patients in the fasting state of the morning. Results: The number of peripheral blood neutrophils, lymphocytes, and HBP was higher in the OSAS group than in the control group, and the differences were statistically significant (P all <.05), while the differences in NLR and PCT between the 2 groups were not statistically significant (P all >.05). Plasma HBP level had an area under the curve (AUC) of 0.79 (P < .0001) in determining OSAS, with a sensitivity of 80.49% and a specificity of 70.83% and the best cutoff value was >10.73 ng/ml. Combining body mass index (BMI), neutrophil, lymphocyte, and HBP improved the predictive value of OSAS with an AUC of 0.89 (P < .0001), a sensitivity of 80.49%, and a specificity of 87.50%. Logistic regression analysis showed that both BMI and HBP were independent risk factors for OSAS (PBMI < .001, PHBP < .01), while neutrophils and lymphocytes were not (P all >.05). Conclusions: This is the first study to objectively examine HBP in OSAS patients, and HBP is an independent risk factor that may serve as a diagnostic biomarker in OSAS. Patients with OSAS have an altered systemic inflammatory state and may be more prone to severe bacterial infections.

Immunomodulatory Effects of Microcin C7 in Cyclophosphamide-Induced Immunosuppressed Mice.

Microcin C7 (McC) as a viable immunomodulator peptide can be a potential solution for pathogenic microbial infection in the post-antibiotic era and has gained substantial attention. This study was designed to evaluate the immunomodulatory activity of Microcin C7 in a cyclophosphamide (CTX)-induced immunodeficient mouse model. We show that Microcin C7 treatment significantly alleviated the CTX-caused body weight loss, improved the feed and water consumption to improve the state of the mice, and elevated the absolute number and proportion of peripheral blood lymphocytes as well as the level of hemoglobulin. We further aim to characterize the phenotypes of the immune function and intestinal health profiles. The results demonstrate that Microcin C7 treatment increased serum levels of immunoglobulin A (IgA), IgG, interleukin 6, and hemolysin, promoted splenic lymphocyte proliferation induced by concanavalin A and LPS, and enhanced the phagocytosis of peritoneal macrophages immunized by sheep red blood cells. Additionally, Microcin C7 treatment decreased levels of diamine oxidase and d-lactate, ameliorated CTX-induced intestinal morphological damage, and increased the levels of zonula occluden 1, occludin, claudin-1, mucin 2, and secretary IgA in the jejunum and colon. Moreover, Microcin C7 administration is sufficient to reverse CTX-induced intestinal microbiota dysbiosis by increasing the number of Lactobacillus and Bifidobacterium, decreasing the number of Escherichia coli in colonic contents. Collectively, our results demonstrate that Microcin C7 may have protective and immunomodulatory functions and could be a potential candidate used in animal feed, functional foods, and immunological regimens..

Effect of gut microbiota homeostasis on hematopoiesis in a neonatal rat model of necrotizing enterocolitis

To study the effect of gut microbiota on hematopoiesis in a neonatal rat model of necrotizing enterocolitis (NEC). Neonatal Sprague-Dawley rats were randomly divided into a control group and a model group (NEC group), with 6 rats in each group. Formula milk combined with hypoxia and cold stimulation was used to establish a neonatal rat model of NEC. Hematoxylin and eosin staining was used to observe the pathological changes of intestinal tissue and hematopoiesis-related organs. Routine blood tests were conducted for each group. Immunohistochemistry was used to observe the changes in specific cells in hematopoiesis-related organs. Flow cytometry was used to measure the changes in specific cells in bone marrow. 16S rDNA sequencing was used to observe the composition and abundance of gut microbiota. Compared with the control group, the NEC group had intestinal congestion and necrosis, damage, atrophy, and shedding of intestinal villi, and a significant increase in NEC histological score. Compared with the control group, the NEC group had significantly lower numbers of peripheral blood leukocytes and lymphocytes (P<0.05), nucleated cells in the spleen, thymus, and bone marrow, and small cell aggregates with basophilic nuclei in the liver (P<0.05). The NEC group had significant reductions in CD71+ erythroid progenitor cells in the liver, CD45+ lymphocytes in the spleen and bone marrow, CD3+ T lymphocytes in thymus, and the proportion of CD45+CD3-CD43+SSChi neutrophils in bone marrow (P<0.05). There was a significant difference in the composition of gut microbiota between the NEC and control groups, and the NEC group had a significant reduction in the abundance of Ligilactobacillus and a significant increase in the abundance of Escherichia-Shigella (P<0.05), which replaced Ligilactobacillus and became the dominant flora. Multi-lineage hematopoietic disorder may be observed in a neonatal rat model of NEC, which may be associated with gut microbiota dysbiosis and abnormal multiplication of the pathogenic bacteria Escherichia-Shigella.

Angelica Sinensis polysaccharide antagonizes 5-Fluorouracil-induced spleen injury and dysfunction by suppressing oxidative stress and apoptosis

Angelica Sinensis polysaccharide (ASP), the main active component of Angelica sinensis, possesses antioxidative and anti-apoptotic properties. In this study, we have investigated the antagonistic effect of ASP on 5-FU-induced injury of mouse spleen in vivo and splenocytes in vitro, and its possible mechanism. Our results showed that ASP inhibited 5-FU-induced decreases in spleen weight and organ index in mice, restored the number of peripheral blood leukocytes and lymphocytes, repaired spleen structure disorder and functional impairment, rescued serum IL-2, IL-6, and IFN-γ levels, and relieved 5-FU-induced mitochondrial swelling， reduced the oxidant accumulation including MDA and ROS, whereas increasing the activities of GSH, SOD and CAT. The mechanism may be related to ASP downregulation of Keap1 protein expression thus motivating the nuclear translocation of Nrf2. Furthermore, ASP alleviated the apoptosis of spleens in vivo and splenocytes in vitro, and reactivated PI3K / AKT signalling. In conclusion, the protective effect of ASP on spleens and splenocytes may be related to the reduction of oxidative stress and apoptosis via reactivation of Nrf2 and PI3K/AKT pathways. This study has provided a new protective agent for minimizing the spleen injury caused by 5-FU and a new idea for improving the prognosis of chemotherapy patients.

Associations between Short-Term Air Pollution Exposure and the Peripheral Leukocyte Distribution in the Adult Male Population in Beijing, China.

The inflammatory effects of air pollution exposure may account for increased public health risk. However, evidence regarding the effects of air pollution on peripheral blood leukocytes in the population is inconsistent. We investigated the association between the short-term effects of ambient air pollution and the peripheral blood leukocyte distribution in adult men in Beijing, China. From January 2015 to December 2019, a total of 11,035 men aged 22-45 years in Beijing were included in the study. Their peripheral blood routine parameters were measured. The ambient pollution monitoring parameters (particulate matter ≤ 10 µm (PM10), PM2.5, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), and ozone (O3)) were collected daily. The potential association between ambient air pollution exposure and peripheral blood leukocyte count and classification was analyzed with generalized additive models (GAMs). After adjusting for confounding factors, PM2.5, PM10, SO2, NO2, O3, and CO were significantly correlated with changes to at least one peripheral leukocyte subtype. Short-term and cumulative air pollutant exposure dramatically increased the participants' peripheral blood neutrophil, lymphocyte, and monocyte numbers and decreased eosinophils and basophils. Our results demonstrated that air pollution induced inflammation in the participants. The peripheral leukocyte count and classification can be utilized to evaluate the inflammation induced by air pollution in the exposed male population.

Assessment of metabolic activity and energy supply of peripheral blood lymphocytes

BACKGROUND: T-cells have the capability to change their metabolism in response to activation signals. Resting T-cells primarily use the oxidation of higher fatty acids and oxidative phosphorylation in mitochondria for their energy needs, whereas activated T-cells switch to aerobic glycolysis and glutaminolysis, using glucose, and glutamine as substrates, respectively.&#x0D; AIM: To determine the metabolic activity and energy supply of peripheral blood lymphocytes in predominantly healthy northerners by measuring the intracellular content of HIF-1 (hypoxia-induced factor 1), SIRT3 (sirtuin 3), and ATP (adenosine triphosphate).&#x0D; MATERIALS AND METHODS: 39 volunteers, residents of the Arkhangelsk region (23 women and 16 men, 2362 years old), were selected, and examined for this experiment. We established the total number of peripheral blood lymphocytes with CD-typing of lymphocytes (CD3+, CD4+, CD8+, CD71+) by indirect immunoperoxidase reactions, the content of HIF-1 and SIRT3 in the lymphocyte lysate employing enzyme immunoassay, the concentration of ATP by luminescent analysis through luciferin-luciferase reaction. Statistical analysis was conducted in "Statistica 10.0", cluster analysis was applied using the k-means method. Mean values (M) and standard deviations (SD) were calculated, the normal distribution was tested by the KolmogorovSmirnov and Lilliefors criterion. Student's t-test was calculated, and the differences were considered statistically significant at p 0.05.&#x0D; RESULTS: The study revealed that the metabolic activity of lymphocytes associated with HIF-1 regulation differs significantly in the examined volunteers,, while in the group with a lower total number of lymphocytes and their subpopulations (CD3+, CD4+, CD8+, CD71+) there is a predominant glycolytic orientation of metabolism with proliferated cells energy supply.&#x0D; CONCLUSION: Metabolic activity which can be determined by the HIF-1/SIRT3 ratio, and the energy supply of lymphocytes have a substantial impact on their differentiation, proliferation, and functioning.

Systemic inflammation in salivary gland cancer

Relevance. The inflammatory process and endogenous intoxication of the patient’s body has a negative impact on the course of many malignant neoplasms, including salivary gland cancer.The objective of the study was to determine the influence of some factors of systemic inflammation and endogenous intoxication in salivary gland cancer.Methods and materials. A prospective study included the data of 59 patients with salivary gland cancer. The influence of peripheral blood parameters and relative indicators characterizing systemic inflammation on overall and disease-free survival was assessed.Results. As a result of the multivariate analysis, it was revealed that an increase in the level of the relative number of peripheral blood neutrophils by more than 60.08 % increases the risk of death in patients from salivary gland cancer by 3.90 times (p=0.0456; HR 3.90: 95 % CI 1.03–14.79). The level of the absolute number of peripheral blood lymphocytes, not exceeding 1.49x109 /l, increases the risk of disease progression by 8.72 times (p=0.0002, R 8.72: 95 % CI 2.78–27.28).Conclusion. Individual factors of systemic inflammation and endogenous intoxication, it is advisable to evaluate at the stage of planning the primary treatment of patients with salivary gland cancer, in order to determine the prognosis of the disease and optimize the choice of tactics for the primary treatment of patients.

Features of the functioning of innate immunity in children with chronic idiopathic urticaria

Aim. To study the features of the functioning of innate immunity in children with chronic idiopathic urticaria.Materials and methods. The study included 28 children of both sexes aged 6–16 years with chronic idiopathic urticaria (CIU). The median age of the patients was 8 years (p = 0.045). Clinical research methods included an analysis of complaints and anamnestic data, as well as an objective examination of the child (dynamics of urticaria, severity of itching, the presence of angioedema). Immunological techniques included determination of the number of monocytes expressing CD14+CD282+, CD14+CD284+, CD14+CD289+, the number of peripheral blood lymphocytes expressing CD3+CD16+, the levels of immunoglobulin (Ig) E, lactoferrin, interferon (IFN) γ, interleukin (IL)4, and IL-6, and a nitroblue tetrazolium test.Results. In the course of the study, an increase in the expression of Toll-like receptors TLR2 and TLR4 by monocytes, a decrease in the expression of TLR9 by monocytes, a significant rise in lactoferrin levels, a slight decrease in the number of natural killer (NK) cells, a decrease in microbicidal activity and adaptive reserves, a rise in IgE levels, a decrease in IL-4 levels, and an increase in IFNγ and IL-6 were revealed in children with CIU.Conclusion. The immunological changes revealed during the study indicate multidirectional expression of Toll-like receptors, disturbances in the work of the cellular components of innate immunity, and a launch of a proinflammatory cytokine cascade in children with CIU, which can serve as a mainstay for the development of new schemes for personalized therapy of CIU in children.

Peripheral blood and bronchoalveolar leukocyte profile in lung transplant recipients and their changes according to immunosuppressive regimen: A single-center experience.

BackgroundAfter lung transplantation (LuTX), lower respiratory tract infections (LRTI) and acute cellular rejection (ACR) are associated with changes in peripheral blood and bronchoalveolar lavage fluid mononuclear cell profile (PBMC and BALIC). PBMC is also influenced by immunosuppressive regimen and its changes with postoperative time. First‐year PBMC and BALIC changes were evaluated in this study with rabbit anti‐thymocyte globulin (ATG) and alemtuzumab (AL) induction therapy.MethodsIn total, 64 LuTX recipients were included, 53 of them received AL and 11 ATG as induction therapy. PBMC and BALIC were examined routinely and in cases suspicious of infection and/or rejection. A PBMC‐ and BALIC‐based algorithm for infection and rejection prediction was also tested.ResultsIn the AL group, peripheral blood lymphocyte and basophil cell numbers were significantly reduced, while the neutrophil cell number elevation during LRTI was significantly higher compared to the control. Early postoperative measurements showed a lower BALIC lymphocyte count. The algorithm had 17% sensitivity and 94% specificity for ACR in all patients and 33% sensitivity and 95% specificity for ACR with coexisting LRTI.ConclusionBALIC is not significantly influenced by the immunosuppressive regimen. PBMC‐ and BALIC‐based algorithm may improve the differential diagnosis of ACR.

Antagonistic effect of selenium on mercuric chloride in the central immune organs of chickens: The role of microRNA-183/135b-FOXO1/TXNIP/NLRP3 inflammasome axis.

Mercury (Hg) is a persistent environmental and industrial pollutant that accumulated in the body and induces oxidative stress and inflammation damage. Selenium (Se) has been reported to antagonize immune organs damage caused by heavy metals. Here, we aimed to investigate the prevent effect of Se on mercuric chloride (HgCl2 )-induced thymus and bursa of Fabricius (BF) damage in chickens. The results showed that HgCl2 caused immunosuppression by reducing the relative weight, cortical area of the thymus and BF, and the number of peripheral blood lymphocytes. Meanwhile, HgCl2 induced oxidative stress and imbalance in cytokines expression in the thymus and BF. Further, we found that thioredoxin-interacting protein (TXNIP) and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome mediated HgCl2 -induced oxidative stress and inflammation. Mechanically, the targeting and inhibitory effect of microRNA (miR)-135b/183 on forkhead box O1 (FOXO1) were an upstream event for HgCl2 -activated TXNIP/NLRP3 inflammasome pathway. Most importantly, Se effectively attenuated the aforementioned damage in the thymus and BF caused by HgCl2 and inhibited the TXNIP/NLRP3 inflammasome pathway by reversing the expression of FOXO1 through inhibiting miR-135b/183. In conclusion, the miR-135b/183-FOXO1/TXNIP/NLRP3 inflammasome axis might be a novel mechanism for Se to antagonize HgCl2 -induced oxidative stress and inflammation in the central immune organs of chickens.

SARS-CoV2 anti-spike IgG response following COVID-19 mRNA vaccination (BNT162b2) in patients with hematological disorders

This is a prospective study conducted to determine the level of anti-spike IgG to SARS-CoV-2 2-6 weeks following the BNT162b2 vaccination in 125 patients with hematological disorders. Compared with healthy controls, patients with malignant lymphoma had lower rates of seropositivity and lower levels of antibody titer. Furthermore, patients who received rituximab (R)-containing chemotherapy had lower antibody titers than those who were not treated with R or who had completed R-containing chemotherapy more than 9 months earlier. Despite having 71% IgG-seropositivity, patients with multiple myeloma had lower antibody titers than the control group. Furthermore, patients receiving daratumumab-containing chemotherapy had lower antibody titers than those not receiving treatment. Moreover, patients with acute myeloid leukemia or myelodysplastic syndrome had lower antibody titers than the control group. Overall, the number of peripheral blood lymphocytes was significantly correlated with IgG titers, with seropositive patients having more peripheral blood lymphocytes than seronegative patients. Patients with severe immunosuppression, such as those with hematological disorders, often have impaired seroconversion with COVID-19 vaccination that should be taken into consideration by clinicians.

Deficiency of eIF4B Increases Mouse Mortality and Impairs Antiviral Immunity.

Eukaryotic translation initiation factor 4B (eIF4B) plays an important role in mRNA translation initiation, cell survival and proliferation in vitro. However, its function in vivo is poorly understood. Here, we identified that eIF4B knockout (KO) in mice led to embryonic lethality, and the embryos displayed severe liver damage. Conditional KO (CKO) of eIF4B in adulthood profoundly increased the mortality of mice, characterized by severe pathological changes in several organs and reduced number of peripheral blood lymphocytes. Strikingly, eIF4B CKO mice were highly susceptible to viral infection with severe pulmonary inflammation. Selective deletion of eIF4B in lung epithelium also markedly promoted replication of influenza A virus (IAV) in the lung of infected animals. Furthermore, we observed that eIF4B deficiency significantly enhanced the expression of several important inflammation-associated factors and chemokines, including serum amyloid A1 (Saa1), Marco, Cxcr1, Ccl6, Ccl8, Ccl20, Cxcl2, Cxcl17 that are implicated in recruitment and activation of neutrophiles and macrophages. Moreover, the eIF4B-deficient mice exhibited impaired natural killer (NK) cell-mediated cytotoxicity during the IAV infection. Collectively, the results reveal that eIF4B is essential for mouse survival and host antiviral responses, and establish previously uncharacterized roles for eIF4B in regulating normal animal development and antiviral immunity in vivo.