The CD40 rs1883832 Polymorphism Affects Sepsis Susceptibility and sCD40L Levels

Sepsis is a severe and progressive disease characterized by systemic inflammatory response syndrome (SIRS). CD40 serves as a vital link between immune response and inflammation. This study was designed to investigate the potential association between a functional single-nucleotide polymorphism (SNP) of CD40 (rs1883832) and susceptibility to sepsis. We first performed a case-control study to explore the relationship between the CD40 rs1883832 polymorphism and sepsis. CD40 mRNA expression and protein expression were determined by real-time PCR and western blotting, respectively, in peripheral blood mononuclear cells (PBMCs) from sepsis patients and healthy controls. The plasma sCD40L levels in the two groups were measured by ELISA. The results showed that the frequencies of the TT genotype and the CD40 rs1883832 T allele were significantly higher in sepsis patients than in healthy controls. Plasma sCD40L levels were also significantly increased in sepsis patients. In addition, TT genotype carriers among sepsis patients displayed the highest CD40 expression at both the mRNA and protein levels, accompanied by the highest plasma sCD40L concentrations. In conclusion, the CD40 rs1883832 T allele acts as a risk factor for increased susceptibility to sepsis and may be involved in the process of sepsis through regulation of CD40 expression and plasma sCD40L levels.

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Increased Levels of Alternatively Spliced Interleukin 4 (IL-4δ2) Transcripts in Peripheral Blood Mononuclear Cells from Patients with Systemic Sclerosis

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.6.5.660-664.1999 ◽

1999 ◽

Vol 6 (5) ◽

pp. 660-664 ◽

Cited By ~ 38

Author(s):

Lazaros I. Sakkas ◽

Charles Tourtellotte ◽

Steve Berney ◽

Allen R. Myers ◽

Chris D. Platsoucas

Keyword(s):

Systemic Sclerosis ◽

Mononuclear Cells ◽

Full Length ◽

Interleukin 4 ◽

Healthy Controls ◽

Peripheral Blood Mononuclear ◽

Protein Levels ◽

Blood Mononuclear Cells ◽

Alternatively Spliced ◽

Ifn Γ

ABSTRACT Recent in vitro studies have shown that interleukin 4 (IL-4) induces and gamma interferon (IFN-γ) inhibits collagen production. To define the TH1(IFN-γ) and TH2(IL-4) cytokine profiles in systemic sclerosis (Sscl), a disease characterized by widespread fibrosis, we investigated IL-4 and IFN-γ transcripts in peripheral blood mononuclear cells and plasma protein levels in 13 patients with Sscl. Two previously identified IL-4 transcripts, a full-length transcript and an alternatively spliced (truncated) transcript (designated IL-4δ2), were identified in patients and normal controls. Significantly increased levels of total IL-4 transcripts (full-length plus IL-4δ2 transcripts) were found in patients with Sscl in comparison to those found in healthy controls (P = 0.003), and this increase was primarily due to an increase in the level of the alternatively spliced IL-4δ2 form. The IL-4δ2/full-length-IL-4 transcript ratio was significantly increased in Sscl patients (P < 0.0001, versus healthy controls). Sequencing analysis revealed that the frequency of IL-4 clones carrying the IL-4δ2 transcript was also substantially increased in patients with Sscl. Plasma IL-4 protein levels were increased in Sscl patients compared to those in healthy controls (P = 0.001) and correlated with total IL-4 transcript levels. The up-regulation of the fibrogenic IL-4 (a TH2 cytokine) in Sscl suggests a pathogenic role for IL-4 in this disease.

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Contribution of hsa-miR-146a and hsa-miR-223 gene variations in patients with multiple sclerosis reveals association of rs2910164 and rs1044165 with risk of multiple sclerosis susceptibility

Journal of Investigative Medicine ◽

10.1136/jim-2020-001539 ◽

2021 ◽

pp. jim-2020-001539

Author(s):

Salar Shareef ◽

Seyed Omar Ebrahimi ◽

Somayeh Reiisi

Keyword(s):

Multiple Sclerosis ◽

Iranian Population ◽

Healthy Controls ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Mirna Genes ◽

Increased Risk ◽

Non Coding Rnas ◽

The Relationship ◽

Control Study

MicroRNAs (miRNAs) are a group of non-coding RNAs that play a role in gene regulation. Due to their possible functional importance, genetic variants within miRNA genes have been recognized as candidate biomarkers. Single-nucleotide polymorphisms (SNPs) in miRNA genes can be related to the risk of different autoimmune diseases. Some of these SNPs are rs2910164 in the miR-146a and rs1044165 in the miR-223. The aim of this study was to investigate the relationship between these polymorphisms and the risk of multiple sclerosis (MS) in an Iranian population. In this case–control study, 261 patients with MS and 250 healthy controls that matched by age and geographical region were enrolled. After sampling and genomic DNA extraction, genotyping was determined by PCR–restriction fragment length polymorphism. Allelic and genotypic associations between the SNPs and MS were evaluated by the data analysis conducted by SPSS V.20. The frequencies of rs2910164 and rs1044165 SNPs were significantly different between the patients with MS and healthy controls. C and T alleles in the variants rs2910164 and rs1044165, respectively, are associated with increased risk of MS. Such association was obtained in codominant, dominant, and overdominant models for both variants (OR ~3 and OR ~1.5, respectively). Furthermore, this study determined that the C and T alleles of rs2910164 and rs1044165 are risk factors for MS in the Iranian population.

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Ovine plasma prion protein levels show genotypic variation detected by C-terminal epitopes not exposed in cell-surface PrPC

Biochemical Journal ◽

10.1042/bj20060746 ◽

2006 ◽

Vol 400 (2) ◽

pp. 349-358 ◽

Cited By ~ 16

Author(s):

Alana M. Thackray ◽

Tim J. Fitzmaurice ◽

Lee Hopkins ◽

Raymond Bujdoso

Keyword(s):

Cell Surface ◽

Mononuclear Cells ◽

Genotypic Variation ◽

Specific Monoclonal Antibody ◽

Peripheral Blood Mononuclear ◽

Protein Levels ◽

Bovine Plasma ◽

Natural Scrapie ◽

Susceptibility And Resistance ◽

Increased Susceptibility

Ovine PBMCs (peripheral blood mononuclear cells) express PrPC [cellular PrP (prion-related protein)] and have the potential to harbour and release disease-associated forms of PrP during scrapie in sheep. Cell-surface PrPC expression by PBMCs, together with plasma PrPC levels, may contribute to the regulatory mechanisms that determine susceptibility and resistance to natural scrapie in sheep. Here, we have correlated cell-surface PrPC expression on normal ovine PBMCs by FACS with the presence of PrPC in plasma measured by capture–detector immunoassay. FACS showed similar levels of cell-surface PrPC on homozygous ARR (Ala136-Arg154-Arg171), ARQ (Ala136-Arg154-Gln171) and VRQ (Val136-Arg154-Gln171) PBMCs. Cell-surface ovine PrPC showed modulation of N-terminal epitopes, which was more evident on homozygous ARR cells. Ovine plasma PrPC levels showed genotypic variation and the protein displayed C-terminal epitopes not available in cell-surface PrPC. Homozygous VRQ sheep showed the highest plasma PrPC level and homozygous ARR animals the lowest. For comparison, similar analyses were performed on normal bovine PBMCs and plasma. PrPC levels in bovine plasma were approx. 4-fold higher than ovine homozygous ARQ plasma despite similar levels of PBMC cell-surface PrPC expression. Immunoassays using C-terminal-specific anti-PrP monoclonal antibodies as capture and detector reagents revealed the highest level of PrPC in both ovine and bovine plasma, whilst lower levels were detected using N-terminal-specific monoclonal antibody FH11 as the capture reagent. This suggested that a proportion of plasma PrPC was N-terminally truncated. Our results indicate that the increased susceptibility to natural scrapie displayed by homozygous VRQ sheep correlates with a higher level of plasma PrPC.

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Downregulation of miR-3934 in Peripheral Blood Mononuclear Cells of Asthmatic Patients and Its Potential Diagnostic Value

BioMed Research International ◽

10.1155/2021/8888280 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Wenyu Wang ◽

Jing Wang ◽

Hong Chen ◽

Xiaofei Zhang ◽

Kaiyu Han

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Diagnostic Value ◽

Healthy Controls ◽

Peripheral Blood Mononuclear ◽

Asthmatic Patients ◽

Blood Mononuclear Cells ◽

Asthma Patients ◽

The Relationship

Background. The present study focused on the potential clinical significance of miR-3934 in the occurrence and development of asthma. Methods. 80 asthma and 80 healthy controls were recruited in this study. The peripheral blood mononuclear cells (PBMCs) and serum samples of the asthma patients as well as the healthy controls were isolated, and the expression levels of miR-3934 in PBMCs were examined by RT-qPCR methods. Furthermore, the relationship between the level of miR-3934 in PBMCs and the disease severity has been analyzed, and the potential diagnostic value of miR-3934 was evaluated by the receiver operating characteristics (ROC) curve. Finally, the expression level of IL-6, IL-8, and IL-33 have been detected using the ELISA kits, and Pearson’s correlation analysis was performed to investigate the relationship between the level of miR-3934 in PBMCs and the serum expression of those inflammatory cytokines in asthma patients. Results. miR-3934 was dramatically decreased in PBMCs of the asthma patients, and miR-3934 was markedly reduced in PBMCs of patients with severe asthma vs. mild asthma. Furthermore, ROC analysis showed that levels of miR-3934 in PBMCs can distinguish asthma patient, especially the severe asthma patients from the controls. Finally, the levels of miR-3934 in PBMCs were negatively correlated with the serum levels of IL-6, IL-8, and IL-33 in asthma patients, respectively. Conclusions. miR-3934 was downregulated in PBMCs of asthmatic patients and may function as a potential diagnosis biomarker.

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COVID-19 Severity Potentially Modulated by Cardiovascular-Disease-Associated Immune Dysregulation

Viruses ◽

10.3390/v13061018 ◽

2021 ◽

Vol 13 (6) ◽

pp. 1018

Author(s):

Abby C. Lee ◽

Grant Castaneda ◽

Wei Tse Li ◽

Chengyu Chen ◽

Neil Shende ◽

...

Keyword(s):

Rna Sequencing ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Expression Profiles ◽

Immune Dysregulation ◽

Left Ventricular ◽

Recurrent Event ◽

Healthy Controls ◽

Sequencing Data ◽

Peripheral Blood Mononuclear

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19.

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The role of CXCR3 and its ligands expression in Brucellar spondylitis

BMC Immunology ◽

10.1186/s12865-020-00390-9 ◽

2020 ◽

Vol 21 (1) ◽

Author(s):

Xin Hu ◽

Xiaoqian Shang ◽

Liang Wang ◽

Jiahui Fan ◽

Yue Wang ◽

...

Keyword(s):

Protein Expression ◽

Mrna Expression ◽

Mononuclear Cells ◽

Healthy Controls ◽

Inflammatory Infiltration ◽

Peripheral Blood Mononuclear ◽

Expression Levels ◽

Inflammatory Damage ◽

Ifn Γ ◽

Mrna Expression Levels

Abstract Aim Brucellar spondylitis (BS) is one of the most serious complications of brucellosis. CXCR3 is closely related to the severity of disease infection. This research aimed to study the degree of BS inflammatory damage through analyzing the expression levels of CXCR3 and its ligands (CXCL9 and CXCL10) in patients with BS. Methods A total of 29 BS patients and 15 healthy controls were enrolled. Real-Time PCR was used to detect the mRNA expression levels of IFN-γ, CXCR3, CXCL9 and CXCL10 in peripheral blood mononuclear cells (PBMCs) of BS patients and healthy controls. Hematoxylin-Eosin staining was used to show the pathological changes in BS lesion tissues. Immunohistochemistry staining was used to show the protein expression levels of Brucella-Ab, IFN-γ, CXCR3, CXCL9 and CXCL10 in BS lesion tissues. At the same time, ELISA was used to detect the serum levels of IFN-γ, CXCL9 CXCL10 and autoantibodies against CXCR3 in patients with BS. Results In lesion tissue of BS patients, it showed necrosis of cartilage, acute or chronic inflammatory infiltration. Brucella-Ab protein was abundantly expressed in close lesion tissue. And the protein expression levels of IFN-γ, CXCR3 and CXCL10 were highly expressed in close lesion tissue and serum of BS patients. At the same time, the mRNA expression levels of IFN-γ, CXCR3 and CXCL10 in PBMCs of BS patients were significantly higher than those in controls. Conclusion In our research, the expression levels of IFN-γ, CXCR3 and its ligands were significantly higher than those in controls. It suggested that high expression levels of IFN-γ, CXCR3 and its ligands indicated a serious inflammatory damage in patients with BS.

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Peripheral Blood Mononuclear Cells Antioxidant Adaptations to Regular Physical Activity in Elderly People

Nutrients ◽

10.3390/nu10101555 ◽

2018 ◽

Vol 10 (10) ◽

pp. 1555 ◽

Cited By ~ 5

Author(s):

Carla Busquets-Cortés ◽

Xavier Capó ◽

Maria Bibiloni ◽

Miquel Martorell ◽

Miguel Ferrer ◽

...

Keyword(s):

Physical Activity ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Regular Physical Activity ◽

Antioxidant Defenses ◽

Active Lifestyle ◽

Peripheral Blood Mononuclear ◽

Protein Levels ◽

Blood Mononuclear Cells

Regular physical activity prescription is a key point for healthy aging and chronic disease management and prevention. Our aim was to evaluate the antioxidant defense system and the mitochondrial status in peripheral blood mononuclear cells (PBMCs) and the level of oxidative damage in plasma in active, intermediate and inactive elderly. In total, 127 healthy men and women >55 years old participated in the study and were classified according on their level of declared physical activity. A more active lifestyle was accompanied by lower weight, fat mass and body mass index when compared to a more sedentary life-style. Active participants exhibited lower circulating PBMCs than inactive peers. Participants who reported higher levels of exercise had increased antioxidant protein levels when compared to more sedentary partakers. Carbonylated protein levels exhibited similar behavior, accompanied by a significant raise in expression of cytochrome c oxidase subunit IV in PBMCs. No significant changes were found in the activities of antioxidant enzymes and in the expression of structural (MitND5) and mitochondrial dynamic-related (PGC1α and Mitofusins1/2.) proteins. Active lifestyle and daily activities exert beneficial effects on body composition and it enhances the antioxidant defenses and oxidative metabolism capabilities in PBMCs from healthy elderly.

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Polymorphisms of Fatty Acid Elongase 2 Gene Afftects Risk of Pulmonary Tuberculosis in China Han Population

Iranian Journal of Public Health ◽

10.18502/ijph.v50i11.7580 ◽

2021 ◽

Author(s):

Min Mu ◽

Li Jing ◽

Yuan-Jie Zou ◽

Xing-Rong Tao ◽

Fei Wang ◽

...

Keyword(s):

Epidemiological Survey ◽

Nucleotide Polymorphism ◽

Dominance Model ◽

Fatty Acid Elongase ◽

Single Nucleotide ◽

Female Population ◽

Genetic Modeling ◽

Male Patients ◽

The Relationship ◽

Control Study

Background: As an infectious disease closely related to Mycobacterium tuberculosis, autoimmunity, inflammation, environment and heredity, the relationship between the single nucleotide polymorphism of elongase 2 gene and the susceptibility to tuberculosis is still unknown. Methods: Between January 2016 and November 2018, a hospital-based case-control study was conducted. This epidemiological survey was conducted in both hospitals every three months. rs3798719, rs1570069, and rs2236212 in ELOVL2 gene were detected by Sanger sequencing. Results: Stratified by gender, the genotypes and allele frequencies of rs3798719, rs1570069 and rs2236212 showed significant differences between the two groups (χ2 = 6.987, P = 0.030), Genetic modeling showed that rs3798719 was statistically different in the overdominance model (χ2 = 4.784, OR = 1.414, 95% CI: 1.036-1.929, P < 0.05). The polymorphism of rs2236212 between male TB patients and healthy controls was statistically different in the dominance model. (χ2 = 4.192, OR = 0.507; 95% CI: 0.262-0.981, P < 0.05). Conclusion: The rs3798719 of ELOVL2 gene may be associated with susceptibility to TB in female population and the rs2236212 of ELOVL2 gene may be associated with TB incidence in male patients.

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Using protein microarray reveals clinical correlation between self-perception of patient and the apoptosis-related proteins in rheumatoid arthritis

10.21203/rs.3.rs-39433/v1 ◽

2020 ◽

Author(s):

Jian-ting Wen ◽

Jian Liu ◽

Hui Jiang ◽

Lei Wan ◽

Ling Xin ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mononuclear Cells ◽

Expression Profiles ◽

Enzyme Linked Immunosorbent Assay ◽

Healthy Controls ◽

Self Perception ◽

Roc Curve Analysis ◽

Peripheral Blood Mononuclear ◽

Related Proteins ◽

Potential Biomarkers

Abstract Background: The most severe effects of rheumatoid arthritis (RA) are loss of physical function, which may have a significant impact on self-perception of patient (SPP). However, the inherent relationship between SPP and the key proteins is not clear. The aim of this study was to get an insight into SPP of RA in connection with the the apoptosis-related proteins. Methods: We set out to investigate changes of the apoptosis-related proteins expression in the peripheral blood mononuclear cells (PBMCs) of RA. Additionally, we aimed to correlate the apoptosis-related proteins expression profiles with SPP and clinical indexes. To this end, we employed antibody microarrays of the the apoptosis-related proteins in PBMCs from four RA patients and seven healthy controls. We used bioinformatics to screen several the apoptosis-related proteins. To validate key protein candidates, we performed Enzyme linked immunosorbent assay (ELISA) on 30 RA patients and 30 healthy controls. Results: We found the expression of ten the apoptosis-related proteins (caspase3, CD40, SMAC, HSP27, HTRA, IGFBP-1, IGFBP-6, sTNF-R1, sTNF-R2, TRAILR-3) were significantly altered in PBMCs of RA patients. Receiver operating characteristic (ROC) curve analysis suggested that these ten the apoptosis-related proteins are potential biomarkers of RA. Spearman Correlation analysis and Logistic-regression analysis revealed that the 10 selected the apoptosis-related proteins correlated with SPP and clinical indexes. Conclusion: Therefore, we highlight some the apoptosis-related proteins may serve as potential biomarkers in prediction of SPP for RA patients, although the underlying mechanisms need to be further explored.

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H3K23/H3K36 hypoacetylation and HDAC1 up-regulation are associated with adverse consequences in obstructive sleep apnea patients

Scientific Reports ◽

10.1038/s41598-021-00052-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yung-Che Chen ◽

Po-Yuan Hsu ◽

Chien-Hung Chin ◽

Chang-Chun Hsiao ◽

Chia-Wei Liou ◽

...

Keyword(s):

Obstructive Sleep Apnea ◽

Sleep Apnea ◽

Mononuclear Cells ◽

Gene Promoter ◽

Peripheral Blood Mononuclear ◽

Protein Levels ◽

Reactive Protein ◽

Primary Snoring ◽

Obstructive Sleep

AbstractThe aim of this study is to determine the roles of global histone acetylation (Ac)/methylation (me), their modifying enzymes, and gene-specific histone enrichment in obstructive sleep apnea (OSA). Global histone modifications, and their modifying enzyme expressions were assessed in peripheral blood mononuclear cells from 56 patients with OSA and 16 matched subjects with primary snoring (PS). HIF-1α gene promoter-specific H3K36Ac enrichment was assessed in another cohort (28 OSA, 8 PS). Both global histone H3K23Ac and H3K36Ac expressions were decreased in OSA patients versus PS subjects. H3K23Ac expressions were further decreased in OSA patients with prevalent hypertension. HDAC1 expressions were higher in OSA patients, especially in those with excessive daytime sleepiness, and reduced after more than 6 months of continuous positive airway pressure treatment. H3K79me3 expression was increased in those with high C-reactive protein levels. Decreased KDM6B protein expressions were noted in those with a high hypoxic load, and associated with a higher risk for incident cardiovascular events or hypertension. HIF-1α gene promoter-specific H3K36Ac enrichment was decreased in OSA patients versus PS subjects. In vitro intermittent hypoxia with re-oxygenation stimuli resulted in HDAC1 over-expression and HIF-1α gene promoter-specific H3K36Ac under-expression, while HDAC1 inhibitor, SAHA, reversed oxidative stress through inhibiting NOX1. In conclusions, H3K23/H3K36 hypoacetylation is associated with the development of hypertension and disease severity in sleep-disordered breathing patients, probably through up-regulation of HDAC1, while H3K79 hypermethylation is associated with higher risk of cardiovascular diseases, probably through down-regulation of KDM6B.

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