MBD2 as a Potential Novel Biomarker for Identifying Severe Asthma With Different Endotypes

Background: Studies have shown that methyl-CpG binding domain protein 2 (MBD2) expression is significantly elevated in a neutrophil-dominant severe asthma mouse model. It also regulates Th17 cell differentiation. The objective of this study was to investigate the relationship between serum MBD2 levels in patients with severe asthma with different endotypes.Methods: Eligible adults with confirmed asthma (n = 63) underwent a clinical assessment, asthma control test and pulmonary function test and were classified as having mild, moderate or severe asthma. Severe asthma endotypes were defined according to the percentage of Th2 and Th17 cells in the peripheral blood and by the type of inflammation. The percentage of Th2 and Th17 cells in the peripheral blood was determined by flow cytometry. Serum MBD2, eosinophilic cationic protein and myeloperoxidase were measured by enzyme-linked immunosorbent assay. Correlations of MBD2 expression with clinical parameters were evaluated using Spearman's rank correlation analysis.Results: Serum MBD2 levels were upregulated in patients with severe asthma compared to healthy controls and patients with mild to moderate asthma. MBD2 was also significantly increased in patients with Th17 severe asthma compared to patients with type 2 severe asthma. Furthermore, MBD2 was positively correlated with MPO and Th17 cells but negatively correlated with ECP and Th2 cells in patients with severe asthma.Conclusions: These findings suggest that serum MBD2 may be a potential new biomarker for identifying severe asthma, Th17 severe asthma and the type of airway inflammation. However, these findings are still preliminary and need to be further investigated.

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Expression and Significance of Th17 Cells and Related Factors in Patients with Autoimmune Hepatitis

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190402160455 ◽

2019 ◽

Vol 22 (4) ◽

pp. 232-237 ◽

Cited By ~ 6

Author(s):

Jihong An

Keyword(s):

Autoimmune Hepatitis ◽

Peripheral Blood ◽

Th17 Cells ◽

Treg Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Serum Total Bilirubin ◽

Study Group ◽

Related Factors ◽

Tnf Α

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.

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Th1 and Th17 Predominance in the Enthesitis-related Arthritis Form of Juvenile Idiopathic Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.081179 ◽

2009 ◽

Vol 36 (8) ◽

pp. 1730-1736 ◽

Cited By ~ 16

Author(s):

ANKIT MAHENDRA ◽

RAMNATH MISRA ◽

AMITA AGGARWAL

Keyword(s):

Juvenile Idiopathic Arthritis ◽

Synovial Fluid ◽

Peripheral Blood ◽

Th17 Cells ◽

Transforming Growth Factor ◽

Health Assessment ◽

Treg Cells ◽

Th2 Cells ◽

Median Frequency ◽

Enthesitis Related Arthritis

Objective.A Th1 biased immune response in synovial fluid has been reported in children with polyarticular and extended oligoarticular-type juvenile idiopathic arthritis (JIA). We investigated T cell phenotypes including Th1, Th2, Th17, and Treg with emphasis on Th17 and Treg, in order to differentiate cytokines in the enthesitis-related arthritis (ERA) form of JIA.Methods.The frequencies of Th1, Th2, Th17, and Treg cells were determined by flow cytometry in peripheral blood (PB) and synovial fluid from patients with ERA and healthy subjects. Levels of interleukin 1ß (IL-1ß), IL-6, IL-21, IL-23, and transforming growth factor ß (TGF-ß), cytokines that influence Th17 lineage cells, were measured in paired plasma and synovial fluid (SF) samples by ELISA. Frequencies are expressed as percentages and cytokine levels as pg/ml.Results.There were no differences in blood samples in the frequency of Th1, Th2, Th17, and Treg cells between patients and controls. In paired samples, the median frequency of CD4+IFN-γ+ (20.49 vs 4.03; p < 0.005) and CD4+IL-17+ (2.27 vs 0.57; p < 0.01) cells was significantly higher in SF compared to PB, respectively; whereas the frequency of CD4+IL-4+ (1.79 vs 2.29; p < 0.04) cells was significantly reduced in the SF compared to PB. There was no difference in the frequency of regulatory T cells. Patients receiving methotrexate had fewer Th2 cells, whereas the Childhood Health Assessment Questionnaire score had a negative association with the frequency of Treg. Median levels of IL-1ß (p < 0.008), IL-6 (p < 0.0001), and IL-17 (p < 0.0001) were higher in SF than in plasma and levels of TGF-ß were lower (p < 0.001). Levels of IL-21 were similar in SF and plasma, whereas IL-23 was undetectable.Conclusion.In patients with ERA, peripheral blood Th1, Th2, Th17, and Treg cells were unchanged, but Th1 and Th17 cells were increased and Th2 cells were reduced in the SF compared to blood. Elevated IL-1ß and IL-6 in SF may be responsible for increased Th17 cells.

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Serum and Saliva 25(OH)D Levels in Relation to Dental Caries in Young Children

Journal of Clinical Pediatric Dentistry ◽

10.17796/1053-4625-45.6.8 ◽

2021 ◽

Vol 45 (6) ◽

pp. 414-420

Author(s):

Alaa Sabah Hussein ◽

Manal Mohamed Almoudi ◽

Mohamed Ibrahim Abu-Hassan ◽

Robert J Schroth ◽

Bahruddin Saripudin ◽

...

Keyword(s):

Dental Caries ◽

Young Children ◽

Rank Correlation ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Children ◽

Spearman’S Rank Correlation ◽

Increased Risk ◽

Whole Saliva ◽

Dmft Index ◽

Unstimulated Whole Saliva

Objective: Several studies have reported that low levels of vitamin D (25(OH)D) are associated with an increased risk of dental caries and that optimal levels may offer protection This study aimed to assess the relationship between serum and saliva 25(OH)D levels and caries among young children. Study design: A total of 120 healthy children were recruited; 93 with caries and 27 caries-free. Dental caries status was evaluated using decayed, missing and filled in primary teeth (dmft) index. Blood and unstimulated whole saliva samples were collected. Laboratory analysis was performed using Enzyme-Linked Immunosorbent Assay Kit. Data were analyzed with descriptive statistics, bivariate and Spearman’s rank correlation analysis. Results: There were no significant associations between serum and saliva 25(OH)D levels and caries status (P > 0.05). Levels of 25(OH)D in serum were significantly higher than levels found in saliva (P < 0.05), and a correlation between serum and saliva 25(OH)D levels was observed (P < 0.05). Conclusions: The association between serum and saliva 25(OH)D and dental caries in young children was inconclusive. However, a positive and significant correlation was observed between serum and saliva 25(OH)D levels. Further studies are warranted to investigate the definite relation between 25(OH)D levels and dental caries and using saliva 25(OH)D as a non-invasive alternative method over blood samples.

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Abnormal expression and clinical significance of 25-hydroxyvitamin D and sFlt-1 in patients with preeclampsia

Journal of International Medical Research ◽

10.1177/0300060519860979 ◽

2019 ◽

Vol 47 (10) ◽

pp. 4673-4682 ◽

Cited By ~ 1

Author(s):

Xinhua Chen ◽

Xuxia Xi ◽

Fan Cui ◽

Ming Wen ◽

Aijuan Hong ◽

...

Keyword(s):

Late Onset ◽

Demographic Data ◽

Rank Correlation ◽

Enzyme Linked Immunosorbent Assay ◽

Lower Serum ◽

Hydroxyvitamin D ◽

Diagnosis And Prognosis ◽

Spearman’S Rank Correlation ◽

Spearman’S Rank Correlation Coefficient ◽

25 Hydroxyvitamin D

Objective To determine the association between levels of serum 25-hydroxyvitamin D (25[OH]D) and soluble fms-like tyrosine kinase 1 (sFlt-1) in patients with preeclampsia. Methods Clinical and demographic data were collected from patients with preeclampsia and healthy pregnant controls. Serum 25(OH)D and sFlt-1 levels were evaluated by enzyme-linked immunosorbent assay and their correlations were determined using Spearman’s rank correlation coefficient. Associations between serum 25(OH)D and sFlt-1 levels and disease severity and clinical parameters were evaluated. Results Significantly lower serum 25(OH)D and higher sFlt-1 levels were observed in patients with preeclampsia ( n = 100) versus controls ( n = 100), and 25(OH)D was inversely correlated with sFlt-1 in patients with preeclampsia. Serum 25(OH)D levels were reduced, while sFlt-1 concentration was increased in patients with severe versus mild preeclampsia. Serum 25(OH)D levels were reduced in late-onset versus early-onset severe preeclampsia. Patients with preeclampsia who had lower serum 25(OH)D or elevated sFlt-1 levels showed significantly higher blood pressure indexes versus those with higher 25(OH)D or lower sFlt-1. Conclusions Low serum 25(OH)D and high sFlt-1 may be candidate biomarkers for preeclampsia diagnosis and prognosis.

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Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation

Journal of Experimental Medicine ◽

10.1084/jem.20082286 ◽

2009 ◽

Vol 206 (11) ◽

pp. 2407-2416 ◽

Cited By ~ 155

Author(s):

Jyoti Das ◽

Guangwen Ren ◽

Liying Zhang ◽

Arthur I. Roberts ◽

Xin Zhao ◽

...

Keyword(s):

Cell Differentiation ◽

Growth Factor ◽

Th17 Cell ◽

Th17 Cells ◽

Molecular Mechanisms ◽

Transforming Growth Factor ◽

Critical Role ◽

Th2 Cells ◽

Th17 Cell Differentiation ◽

Th1 And Th2

Interleukin (IL)-17–producing T helper (Th17) cells play a critical role in the pathophysiology of several autoimmune disorders. The differentiation of Th17 cells requires the simultaneous presence of an unusual combination of cytokines: IL-6, a proinflammatory cytokine, and transforming growth factor (TGF) β, an antiinflammatory cytokine. However, the molecular mechanisms by which TGF-β exerts its effects on Th17 cell differentiation remain elusive. We report that TGF-β does not directly promote Th17 cell differentiation but instead acts indirectly by blocking expression of the transcription factors signal transducer and activator of transcription (STAT) 4 and GATA-3, thus preventing Th1 and Th2 cell differentiation. In contrast, TGF-β had no effect on the expression of retinoic acid receptor–related orphan nuclear receptor γt, a Th17-specific transcription factor. Interestingly, in Stat-6−/−T-bet−/− mice, which are unable to generate Th1 and Th2 cells, IL-6 alone was sufficient to induce robust differentiation of Th17 cells, whereas TGF-β had no effect, suggesting that TGF-β is dispensable for Th17 cell development. Consequently, BALB/c Stat-6−/−T-bet−/− mice, but not wild-type BALB/c mice, were highly susceptible to the development of experimental autoimmune encephalomyelitis, which could be blocked by anti–IL-17 antibodies but not by anti–TGF-β antibodies. Collectively, these data provide evidence that TGF-β is not directly required for the molecular orchestration of Th17 cell differentiation.

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Decreased Breg/Th17 Ratio Improved the Prognosis of Patients with Ulcerative Colitis

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2018/5760849 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Xue Bing ◽

Liang Linlang ◽

Chen Keyan

Keyword(s):

Ulcerative Colitis ◽

Peripheral Blood ◽

Theoretical Basis ◽

Th17 Cells ◽

Colonic Mucosa ◽

Quantitative Polymerase Chain Reaction ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

T Helper 17 ◽

Gene Expressions

Objective. To investigate the effects of regulatory B (Breg) cells and T helper 17 (Th17) cells on pathogenesis of ulcerative colitis, explore the clinical significance of Breg/Th17 ratio on the prognosis of ulcerative colitis, and provide the theoretical basis for the targeted therapy, diagnosis, and prognosis of the disease. Methods. Peripheral blood and colonic mucosa were collected from patients with ulcerative colitis. Hematoxylin-eosin staining was used to observe the pathological changes of colonic mucosa. Flow cytometry was utilized to analyze the percentages of Breg cells and Th17 cells. Real-time fluorescent quantitative polymerase chain reaction and immunohistochemistry were applied to determine the expression of Breg cells-related cytokines IL-10 and Th17 cell transcription factor RORγT. Enzyme-linked immunosorbent assay was employed to detect serum IL-10 and IL-17 levels. Results. The colonic mucosa of ulcerative colitis patients presented massive inflammatory cell infiltration and hemorrhagic necrosis. The number of Breg cells and Th17 cells, the gene expressions of IL-10 and RORγT, and serum levels of IL-10 and IL-17 all increased in peripheral blood. Compared with nonremission group, the remission group showed that the percentage of Breg cells reduced, the percentage of Th17 cells increased, and thus the B10/Th17 ratio was significantly decreased in peripheral blood. In addition, serum IL-10 levels diminished, IL-17 levels increased, and thus IL-10/IL-17 ratio was remarkably reduced in remission group. B10/Th17 ratio and IL-10/IL-17 ratio were positively correlated with the severity of disease. Conclusions. Breg and Th17 cells participate in the occurrence and development of ulcerative colitis. B10/Th17 ratio and IL-10/IL-17 ratio can be used as prognostic markers for ulcerative colitis. This provides a theoretical basis for design of targeted treatment and prognosis assessment of the disease.

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Effects of thermal ablation on Treg/Th17 in hepatocellular carcinoma of mice

European Journal of Inflammation ◽

10.1177/2058739219832489 ◽

2019 ◽

Vol 17 ◽

pp. 205873921983248

Author(s):

Shengchuan Huang ◽

Nina Qu ◽

Yanming Men ◽

Zhen Liu

Keyword(s):

Hepatocellular Carcinoma ◽

Peripheral Blood ◽

Thermal Ablation ◽

Th17 Cells ◽

Treg Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Group Model ◽

Mrna Levels ◽

Model Group ◽

Tumor Tissues

The study was aimed to explore the possible function of thermal ablation treatment on T helper 17 (Th17) cells and regulatory T (Treg) cells in transplantation of hepatocellular carcinoma in mice. In total, 60 male C57BL/6 mice were divided into control group, model group, and treat group. Flow cytometry was used to detect the frequency of Th17 and Treg cells in peripheral blood. The levels of interleukin (IL)-17, IL-23, IL-10, and transforming growth factor beta (TGF-β) in serum were detected by enzyme-linked immunosorbent assay (ELISA).The levels of IL-17, RORγt, Foxp3, and TGF-β mRNA in tumor tissues were detected by real-time fluorescence quantitative PCR (qRT-PCR). Compared with the model group, tumor size was significantly decreased after thermal ablation treatment. After treatment, the frequency of Th17 cells in peripheral blood was significantly decreased, while the frequency of Treg cells was profoundly increased ( P < 0.05). The levels of IL-17 and IL-23 were significantly downregulated, while IL-10 and TGF-β levels were upregulated ( P < 0.05). IL-17 and RORγt mRNA levels in tumor tissues were significantly decreased ( P < 0.05), and Foxp3 and TGF-β mRNA levels were significantly increased ( P < 0.05). Thermal ablation treatment plays a positive role in the treatment of hepatoma in mice through affecting the imbalance of Th17/Treg cells.

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Decreased IL-27 Negatively Correlated with Th17 Cells in Non-Small-Cell Lung Cancer Patients

Mediators of Inflammation ◽

10.1155/2015/802939 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Minchao Duan ◽

Zhengqing Ning ◽

Zhijun Fu ◽

Jianquan Zhang ◽

Guangnan Liu ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Th17 Cells ◽

Quantitative Polymerase Chain Reaction ◽

Small Cell ◽

Enzyme Linked Immunosorbent Assay ◽

Small Cell Lung ◽

Nsclc Patients

The presence of Th17 cells and IL-27 is observed in a variety of inflammatory associated cancers. However, there are some data on the role of Th17 cells and IL-27 in the regulation of immune reactions in non-small-cell lung cancer (NSCLC). The aim of this study is to assess the variation of Th17 cells and IL-27 in the peripheral blood (PB) of patients with NSCLC. The proportion of Th17 cells in peripheral blood mononuclear cells (PBMCs) was evaluated by flow cytometry. The serum concentrations of IL-27 and IL-17 were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expression of RORγt and IL-27 in the peripheral blood was examined by real-time quantitative polymerase chain reaction (QPCR). Expression of IL-27 was lower in NSCLC patients compared with normal controls. The frequency of Th17 cells was increased in NSCLC patients, accompanied by the upregulation of IL-17 and RORγt. IL-27 negatively correlated with the number of Th17 cells and the RORγt mRNA. Our results indicate that IL-27 might inhibit Th17 differentiation in NSCLC patients and better understanding of the regulatory effects of IL-27 on Th17 cells may shed light on potential new targets in cancer prevention and therapy.

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MBD2 Regulates Th17 Cell Differentiation and Experimental Severe Asthma by Affecting IRF4 Expression

Mediators of Inflammation ◽

10.1155/2017/6249685 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Aijun Jia ◽

Yueling Wang ◽

Wenjin Sun ◽

Bing Xiao ◽

Yan Wei ◽

...

Keyword(s):

Cell Differentiation ◽

Protein Expression ◽

Severe Asthma ◽

Epigenetic Regulation ◽

Th17 Cell ◽

Th17 Cells ◽

Neutrophil Infiltration ◽

Neutrophil Granulocyte ◽

Th17 Cell Differentiation ◽

Significant Difference

Th17 cells and IL-17 participate in airway neutrophil infiltration characteristics in the pathogenesis of severe asthma. Methyl-CpG binding domain protein 2 (MBD2) expression increased in CD4+ T cells in peripheral blood samples of asthma patients. However, little is known about that epigenetic regulation of MBD2 in both immunological pathogenesis of experimental severe asthma and CD4+ T cell differentiation. Here, we established a neutrophil-predominant severe asthma model, which was characterized by airway hyperresponsiveness (AHR), BALF neutrophil granulocyte (NEU) increase, higher NEU and IL-17 protein levels, and more Th17 cell differentiation. In the model, MBD2 and IRF4 protein expression increased in the lung and spleen cells. Under overexpression or silencing of the MBD2 and IRF4 gene, the differentiation of Th17 cells and IL-17 secretion showed positive changes. IRF4 protein expression showed a positive change with overexpression or silencing of the MBD2 gene, whereas there was no significant difference in the expression of MBD2 under overexpression or silencing of the IRF4 gene. These data provide novel insights into epigenetic regulation of severe asthma.

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Comparative evaluation of serum calcitonin gene related peptide level in patients with migraine headache with and without aura

10.21203/rs.3.rs-201874/v1 ◽

2021 ◽

Author(s):

Mostafa Rezaee ◽

Nahid Ashja zadeh ◽

Sadegh Izedi ◽

Farinaz Fakhri

Keyword(s):

Correlation Coefficient ◽

Rank Correlation ◽

Calcitonin Gene Related Peptide ◽

Clinical Findings ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Serum Calcitonin ◽

Related Peptide ◽

Spearman’S Rank Correlation ◽

Calcitonin Gene

Abstract Background During a migraine attack, trigeminal activation results in the release of calcitonin gene-related peptide (CGRP), which stimulates the release of inflammatory cytokines playing an important role in migraine. We analyze the serum level of CGRP between two groups of migrainous patients (with aura and without aura) Materials and Methods Thirty six migraine patients (included 18 patients with aura and 18 without aura) additionally 18 healthy volunteers consisted control group were selected from the clinic of Neurology, Shiraz University of Medical Sciences, Shiraz, Iran, between March 2020 and November 2020. The CGRP level were determined from the sera of patients with migraine and control subjects by enzyme-linked immunosorbent assay kits. Spearman's rank correlation coefficient was also determined to calculate the correlation between CGRP and clinical findings. Results The level of CGRP in groups were significantly different between groups (P = 0.00). Also, the level of CGRP in aura group were significantly higher than non-aura group (P = 0.045). The Spearman’s correlation coefficient revealed a positive and significant correlation between the CGRP concentration and age (p = 0.042, r = 0.172), BMI (p = 0.013, r = 0.08), VAS (P = 0.006 ,r = 0.09), frequency of attacks (p = 0.005, r = 0.9), duration of each attack (p = 0.016, r = 0.23), Migraine Disability Assessment Scale.(p = 0.00, r = 0.785), average of number of Medication (p = 0.00, r = 0.694). However, no significant correlation was observed with gender. (P > 0.05 ) Conclusions In our study, we found migraine patients had a higher CGRP level than healthy controls and the level of CGRP was related significantly with the duration, BMI, frequency of headache, age, number of headaches per day. In conclusion, our results confirmed that CGRP may be involved in the pathogenesis of migraine attacks and related with the multiple clinical characteristics.

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