scholarly journals T-bet syndrome-associated bronchial asthma phenotype

2020 ◽  
Vol 22 (1) ◽  
pp. 181-186
Author(s):  
L. N. Sorokina ◽  
V. N. Mineev ◽  
A. V. Eremeeva ◽  
M. A. Nyoma
Keyword(s):  
Transcription Factor ◽  
Bronchial Asthma ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Young Patients ◽  
Control Group ◽  
Excess Body Weight ◽  
Endocrine Disorders ◽  
Peripheral Blood Mononuclear ◽  
Genetically Determined

We aimed to evaluate a significance of T-bet transcription factor in bronchial asthma (BA). A total of 102 patients with BA were examined. The control group was represented by healthy subjects (21 people). The study model was represented by peripheral blood mononuclear cells isolated in a density gradient with standard method. It was found that some patients were characterized by high levels of transcription factor T-bet expression (T-bet > 1.0). The bronchial asthma patients with increased T-bet expression were moir often characterized by the severe disease, requiring therapy with systemic glucocorticoids and β2-agonists, did not have genetic predisposal for allergic diseases, the majority of them had excess body weight and concomitant morbidity (mainly, cardiovascular, gastrointestinal and endocrine disorders). The study of rs324011 polymorphism of STAT6 protein gene in these patients revealed CC and CT genotypes, mostly observed in severe BA. Moreover, they were observed in 100% patients with severe clinical course of BA. A positive correlation was found between the number of T allele presentation in loci, and BA severity (r = 0.88, p = 0.002), as well as between the distribution by genotype (CC-CT/TT), and absolute (counts per one L), and relative (%) number of eosinophils in the sputum (r = 0.79, p = 0.034). The detected associations may be referred to as “T-bet elevation syndrome”, being based on the phenomenon of “genetically determined heterogeneity of signaling system defects”. In individuals with an increased T-bet expression, a significant elevation of transcription factors STAT6 and STAT4 was also detected. Taken together, the presented data indicate that this phenomenon reflects a disturbance of the Th1 / Th2 balance, due to increase in both Th1 and Th2 transcriptional activity. Thus, the patients with bronchial asthma with increased expression of T-bet transcription factor revealed a symptom complex, which we have called “T-bet elevation syndrome” (T-bet > 1.0), which is characterized mainly by severe disease and a certain phenotype of patients. Most likely, this feature is caused by genetically determined defects of signaling systems. High T-bet expression has been observed in young patients with mild BA and can be a prognostic sign.

Changes of IL-4 and IFN-g expression in monocytes and T-helper lymphocytes while modeling of systemic juvenile idiopathic arthritis in Wistar rats

2018 ◽  
pp. 61-69
Author(s):  
В.Н. Сахаров ◽  
П.Ф. Литвицкий ◽  
Е.И. Алексеева ◽  
Н.А. Маянский ◽  
Р.Ш. Закиров
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood Mononuclear Cells ◽  
Wistar Rats ◽  
Mononuclear Cells ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Treatment Groups ◽  
Blood Mononuclear Cells ◽  
T Helpers

Цель исследования - изучение перепрограммирования мононуклеарных лейкоцитов на модели системного ювенильного идиопатического артрита (сЮИА), воспроизводимой у крыс Wistar с использованием полного адъюванта Фрейнда и липополисахарида. Методика. сЮИА воспроизведен у 6-месячных крыс-самцов Wistar. На 40-е сут. эксперимента животные были разделены на 3 группы: 1-я группа - контроль; 2-я - группа доксициклина; 3-я - группа дексаметазона. Взятие проб крови у животных проводили на нулевые, 41-е и 55-е сут. Мононуклеарные клетки периферической крови выделяли гравиметрически, после чего окрашивали их на маркеры и внутриклеточные цитокины. Дифференцировали моноциты (CD3-CD4+) и Т-хелперы (CD3+CD4+). Анализировали динамику внутриклеточной экспрессии интерлейкина IL-4 (рассматривали как маркер про-М2 фенотипа, так как в случае выделения из клетки ИЛ-4 служит стимулятором М2 поляризации макрофагов) и IFN-g (как маркер про-М1 фенотипа) по данным проточной цитофлуориметрии. Применяли непараметрический статистический тест Mann-Whitney-Wilcoxon в программе R для статистической обработки данных. Результаты и заключение. При моделировании сЮИА выявлено закономерное изменение фенотипа моноцитов. Применение же доксициклина и дексаметазона приводило к более ранней поляризации их по про-М2-пути в отношении моноцитов (на 41-е сут.) в сравнении с контролем. Про-М1 эффект (на 55-е сут., в сравнении с контролем) выявлен также в группах доксициклина и дексаметазона. У животных разных групп обнаружены характерные динамические изменения внутриклеточной экспрессии цитокинов. Важно, что различная направленность поляризации фенотипа при сЮИА и применении препаратов наблюдается не только у моноцитов, но и у Т-хелперов. The study objective was to evaluate targeted reprogramming of peripheral blood mononuclear cells in systemic juvenile idiopathic arthritis (sJIA) modeled in 6-month-old male Wistar rats by co-administration of complete Freund’s adjuvant and lipopolysaccharide. Methods. On day 40 of the experiment, rats were divided into three groups: control, doxycycline, and dexamethasone groups. Blood samples were collected on days 0, 41, and 55. Peripheral blood mononuclear cells were isolated gravimetrically and stained for markers and cytokines. Monocytes (CD3-CD4+) and T-helpers (CD3+CD4+) were differentiated as target cells. IL-4 was considered a marker for the pro-M2 phenotype since IL-4 can activate M2 macrophage polarization; IFN-g was considered a marker for the pro-M1 phenotype. Time-related changes in the intracellular expression of IL-4 and IFN-g were studied using flow cytometry. Data were analyzed using nonparametric statistical tests (Mann-Whitney-Wilcoxon) in the R environment for statistical computing. Results and conclusions. Monocytes (like macrophages) underwent reprogramming during the development of modeled sJIA disease. In monocytes of doxycycline and dexamethasone treatment groups, pro-M2 effects were observed earlier (day 41) than in the control group. Pro-M1 effects were observed in monocytes of doxycycline and dexamethasone groups on day 55, as compared with the control group. Characteristic time-related changes of intracellular cytokine expression were described for different groups. Importantly, the differently directed phenotype polarization was observed in sJIA and treatment groups for both monocytes and T-helpers.

Assessment of Key Elements in the Innate Immunity System Among Patients with HIV, HCV, and Coinfections of HIV/HCV

2020 ◽  
Vol 18 (3) ◽  
pp. 194-200
Author(s):  
Maryam Moradi ◽  
Alireza Tabibzadeh ◽  
Davod Javanmard ◽  
Saied Ghorbani ◽  
Farah Bokharaei-Salim ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Mononuclear Cells ◽  
Hiv Infections ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Hiv Coinfection ◽  
Tnf Α ◽  
Immunity Genes ◽  
Healthy Control ◽  
Hcv Coinfection

Background: Coinfection of Hepatitis C virus (HCV) with human immunodeficiency virus (HIV) has a higher risk of mortality than HCV or HIV monoinfection. HCV and HIV infections are specified by systemic inflammation, but the inflammation process in HCV/HIV coinfection is much complicated and is not well characterized. Objective: The aim of this study was to analyze the expression of TLR-3, TLR-7, IL-10, IFN-1 (IFN-α, IFN-β), and TNF-α in HIV, HCV and HIV/HCV co-infected patients. Methods: Forty-five patients including HIV group (n=15), HCV group (n=15), HIV/HCV coinfection group (n=15) and healthy control group (n=15) participated. Peripheral blood mononuclear cells (PBMCs) were obtained. PBMC-RNA, HCV and HIV RNA were extracted from all subjects and cDNA was synthesized. The viral load analyzed by reverse transcription-quantitative PCR (RT-qPCR), and the expression levels of IFN-α, IFN-β, TLR-3, TLR-7, TNF, and IL-10 mRNA were quantified in PBMCs. Results: The levels of IFN-I, IL-10, and TNF-α were overexpressed in all patients’ groups (P<0.05), TLR-7 was upregulated in all groups, but this upregulation was not statistically significant (p>0.05). TLR-3 showed a decrease in all patient groups (P<0.05). The statistical analysis demonstrated that TLR-3 has a negative correlation with HIV load, whereas other genes positively correlated with HIV load. In addition, TLR-3, TNF-α, and IFN-I were negatively correlated with HCV load, whereas TLR-7 and IL-10 s were positively correlated with HCV load. Conclusion: Our results showed a significant relationship between the expression level of innate immunity genes and inflammation in HCV, HIV, and HIV/HCV coinfected patients.

scholarly journals Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients with No-Option Critical Limb Ischemia

2021 ◽  
Vol 10 (10) ◽  
pp. 2213
Author(s):  
Alessia Scatena ◽  
Pasquale Petruzzi ◽  
Filippo Maioli ◽  
Francesca Lucaroni ◽  
Cristina Ambrosone ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Critical Limb Ischemia ◽  
Diabetic Foot ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Limb Ischemia ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

scholarly journals Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 514
Author(s):  
Denise Utami Putri ◽  
Cheng-Hui Wang ◽  
Po-Chun Tseng ◽  
Wen-Sen Lee ◽  
Fu-Lun Chen ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Cells ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Severe Disease ◽  
Viral Rna ◽  
Disease Course ◽  
Peripheral Blood Mononuclear ◽  
Peripheral Immune Cells ◽  
Cell Profile

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.

scholarly journals Single-cell multi-omics analysis of the immune response in COVID-19

2021 ◽  
Author(s):  
Emily Stephenson ◽  
◽  
Gary Reynolds ◽  
Rachel A. Botting ◽  
Fernando J. Calero-Nieto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Single Cell ◽  
Mononuclear Cells ◽  
Severe Disease ◽  
Effector Memory ◽  
Peripheral Blood Mononuclear ◽  
Cross Sectional ◽  
Hematopoietic Stem ◽  
Symptomatic Disease

AbstractAnalysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.

Cellular Bioenergetic and Metabolic Changes in Patients with Autism Spectrum Disorder

2021 ◽  
Vol 21 ◽  
Author(s):  
Maria Gevezova ◽  
Danail Minchev ◽  
Iliana Pacheva ◽  
Yordan Sbirkov ◽  
Ralitsa Yordanova ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Mononuclear Cells ◽  
Cell Metabolism ◽  
Strong Dependence ◽  
Autism Spectrum ◽  
Metabolic Changes ◽  
Spectrum Disorder ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
And Gender

Background: Although Autism Spectrum Disorder (ASD) is considered a heterogeneous neurological disease in childhood, a growing body of evidence associates it with mitochondrial dysfunction explaining the observed comorbidities. Introduction: The aim of this study is to identify variations in cellular bioenergetics and metabolism dependent on mitochondrial function in ASD patients and healthy controls using peripheral blood mononuclear cells (PBMCs). We hypothesized that PBMCs may reveal the cellular pathology and provide evidence of bioenergetic and metabolic changes accompanying the disease. Method: PBMC from children with ASD and a control group of the same age and gender were isolated. All patients underwent an in-depth clinical evaluation. A well-characterized cohort of Bulgarian children was selected. Bioenergetic and metabolic studies of isolated PBMCs were performed with a Seahorse XFp analyzer. Result: Our data show that PBMCs from patients with ASD have increased respiratory reserve capacity (by 27.5%), increased maximal respiration (by 67%) and altered adaptive response to oxidative stress induced by DMNQ. In addition, we demonstrate а strong dependence on fatty acids and impaired ability to reprogram cell metabolism. The listed characteristics are not observed in the control group. These results can contribute to a better understanding of the underlying causes of ASD, which is crucial for selecting a successful treatment. Conclusion: The current study, for the first time, provides a functional analysis of cell bioenergetics and metabolic changes in a group of Bulgarian patients with ASD. It reveals physiological abnormalities that do not allow mitochondria to adapt and meet the increased energetic requirements of the cell. The link between mitochondria and ASD is not yet fully understood, but this may lead to the discovery of new approaches for nutrition and therapy.

scholarly journals Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome

Cholesterol ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Zahra Tavoosi ◽  
Hemen Moradi-Sardareh ◽  
Massoud Saidijam ◽  
Reza Yadegarazari ◽  
Shiva Borzuei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Mononuclear Cells ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Regulation Mechanism ◽  
Healthy Individuals ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Abca1 Expression

ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran) during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75%) compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (P<0.05). Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression.

scholarly journals Hemodialysis-Related Lymphomononuclear Release of Interleukin-12 in Patients with End-Stage Renal Disease

1999 ◽  
Vol 10 (10) ◽  
pp. 2171-2176 ◽  
Author(s):  
BRUNO MEMOLI ◽  
LUIGI MARZANO ◽  
VINCENZO BISESTI ◽  
MICHELE ANDREUCCI ◽  
BRUNA GUIDA
Keyword(s):  
Mononuclear Cells ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Mitogen Stimulation ◽  
Ifn Γ ◽  
Uremic Patients ◽  
Stage Renal Disease ◽  
End Stage

Abstract. Interleukin-12 (IL-12) is a cytokine produced by peripheral blood mononuclear cells (PBMC) that causes interferon-γ (IFN-γ) production and enhancement of cell-mediated cytotoxicity. To clarify the role of hemodialysis biocompatibility on IL-12 production and uremic immunodeficiency, we have studied the IL-12 and IFN-γ release by PBMC harvested from 12 patients dialyzed with cuprophan membrane (CU), eight patients dialyzed with polymethylmethacrylate membrane (PMMA), and eight nondialyzed uremic patients (UR). Ten healthy subjects constituted the control group (CON). PBMC were cultured for 48 h with and without nonspecific mitogen stimulation. In unstimulated conditions, CU showed an IL-12 PBMC production higher than CON, UR, and PMMA (46.67 ± 30.13versus2.56 ± 1.38, 6.16 ± 7.09, and 4.62 ± 4.76 pg/ml, respectively;P< 0.01). IL-12 production was correlated with C3a concentration measured at the outlet of hemodialyzer after 15 min of dialysis (r= 0.69,P< 0.01). IL-12 release in CU remained unchanged under mitogen stimulation (44.34 ± 23.86 pg/ml) and was lower than in CON, UR, and PMMA (66.0 ± 12.41, 68.37 ± 25.78, and 67.75 ± 22.61 pg/ml, respectively;P< 0.05). IFN-γ production was similar, in unstimulated conditions, in all groups. Under stimulation, IFN-γ release was lower in CU (13.42 ± 12.04 IU/ml) than in CON, UR, and PMMA (51.84 ± 30.74, 32.16 ± 13.86, and 32.16 ± 13.86 IU/ml, respectively;P< 0.01). These results demonstrate that hemodialysis with CU induces monocyte activation with an enhanced release of IL-12. On the contrary, stimulated PBMC production of both IL-12 and IFN-γ is lower in these patients than in CON, UR, and PMMA. The altered release of these cytokines could play a role in cell-mediated immunodeficiency of the uremic patients dialyzed with CU.

Sign in / Sign up

Export Citation Format

Share Document