scholarly journals Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2035
Author(s):  
Kuang-Che Kuo ◽  
Ya-Ling Yang ◽  
Mao-Hung Lo ◽  
Xin-Yuan Cai ◽  
Mindy Ming-Huey Guo ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Coronary Arteries ◽  
Caspase 3 ◽  
Methylation Status ◽  
Ivig Treatment ◽  
Mrna Levels ◽  
Real Time Quantitative Pcr ◽  
Control Subjects ◽  
Caspase 1 ◽  
Peripheral Leukocytes

Background: Kawasaki disease (KD) is a form of febrile vasculitis that primarily occurs in children. It can cause inflammation of the coronary arteries, which leads to aneurysms. The pathogenesis of coronary arteries may be associated with apoptosis or pyroptosis mediated by caspases activity, but this idea has not been discussed much in KD. Materials and Methods: We enrolled 236 participants in this study. In the Affymetrix GeneChip® Human Transcriptome Array 2.0 study, there were 18 KD patients analyzed prior to receiving intravenous immunoglobulin (IVIG) treatment, at least 3 weeks after IVIG treatment, and 36 non-KD control subjects. We also recruited 24 KD patients prior to receiving IVIG treatment, at least 3 weeks after IVIG treatment, and 24 non-KD control subjects for Illumina HumanMethylation450 BeadChip study. A separate cohort of 134 subjects was analyzed to validate real-time quantitative PCR. Results: The mRNA levels of caspase-1, -3, -4, and -5 were significantly increased in KD patients compared with control subjects (p < 0.05). After administration of IVIG, the expression of these genes decreased considerably. Of particular note, the methylation status of the CpG sites of the caspase-4 and -5 genes demonstrated significant opposite tendencies between the KD patients and controls. Furthermore, compared with patients who responded to IVIG, refractory KD patients had a lower expression of the caspase-3 gene prior to IVIG treatment. Conclusion: Our study is the first to report the upregulation of pyroptotic caspase-1, -4, and -5 in peripheral leukocytes of KD patients. Moreover, the expression of caspase-3 may be associated with IVIG resistance in KD.

4311Decreased CD177 expression and its association with intravenous immunoglobulin resistance in Kawasaki disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Huang
Keyword(s):  
Kawasaki Disease ◽  
Intravenous Immunoglobulin ◽  
Methylation Status ◽  
Area Under The Curve ◽  
Acute Stage ◽  
Ivig Treatment ◽  
Mrna Levels ◽  
Real Time Quantitative Pcr ◽  
Ivig Resistance ◽  
Intravenous Immunoglobulin Resistance

Abstract Kawasaki disease (KD) is the most common acute coronary vasculitis disease occurring in children. Its occurrence has been attributed to the combined effects of infection, genetics, and immunity. While the etiopathogenesis of KD remains unknown, we have performed a survey of global genetic DNA methylation status and transcripts expression in KD patients to address how they contribute to the pathogenesis of KD. Methods We recruited 148 participants for this study. The chip studies consisted of 18 KD patients that were analyzed prior to administering intravenous immunoglobulin (IVIG) treatment and at least 3 weeks afterward, as well as 36 non-KD control subjects. We performed a separate cohort of 94 subjects to validate real-time quantitative PCR. Results According to the microarray study, CD177, a neutrophil surface molecule, appeared to be most significantly upregulated in KD patients compared to controls with epigenetic hypomethylation. After patients received IVIG treatment, CD177 mRNA levels decreased significantly. PCR validation indicated that the expression of CD177 is consistent with the Transcriptome Array 2.0 results. Furthermore, the area under the curve values of CD177 between KD patients and controls is 0.937. We also observed significantly higher CD177 levels in typical KD than incomplete presentation, which was associated with IVIG resistance in KD patients. Conclusion The present study is the first to highlight the epigenetic hypomethylation of an increased CD177 transcript during the acute stage of KD. Furthermore, the higher expression of CD177 in a typical presentation of KD patients and was related to IVIG resistance.

scholarly journals Differential Expression of TXNIP Isoforms in the Peripheral Leukocytes of Patients with Acute Myocardial Infarction

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yujing Zhang ◽  
Peng Zhong ◽  
Yingze Xu ◽  
Baokui Wang ◽  
Tao Zhu ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Venous Blood ◽  
Mrna Levels ◽  
Endogenous Inhibitor ◽  
Interacting Protein ◽  
Thioredoxin Interacting Protein ◽  
Real Time Quantitative Pcr ◽  
The Difference ◽  
Peripheral Leukocytes

Background. Acute myocardial infarction (AMI) is the most serious type of coronary atherosclerotic heart disease (CAD). The pathological changes are characterized by atherosclerosis. Oxidative stress plays an important role in atherosclerosis. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor and regulator of thioredoxin, could bind thioredoxin to regulate its expression and antioxidant activity negatively. The NCBI data show that there are two isoforms in TXNIP gene, namely, TXNIP1 and TXNIP2. Our previous studies have shown that TXNIP expression levels in patients with unstable angina pectoris (UAP) were increased compared with controls (CTR). However, no upregulation of TXNIP was detected in AMI patients. Methods. The leucocytes were isolated from peripheral venous blood, and total RNA of the leucocytes was extracted. Then, real-time quantitative PCR was performed. Results. mRNA levels of TXNIP2 in AMI were significantly increased compared with CTR (P<0.05). However, the expression of TXNIP1 was downregulated in AMI, but the difference was not statistically significant (P>0.05). Logistic regression analysis showed that TXNIP2 mRNA levels were significantly associated with AMI (OR = 2.207, P<0.05). Conclusions. The expression of TXNIP2, not TXNIP1, is upregulated in leukocytes of AMI patients, indicating that only TXNIP2 in circulating leucocytes may be involved in the pathogenesis of AMI.

Abstract 36: FCGR2A Promoter Methylation and Risks for IVIG Unresponsiveness in Kawasaki Disease

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Ho-Chang Kuo ◽  
Kai-Sheng Hsieh ◽  
Wei-Chiao Chang ◽  
Keyword(s):  
Kawasaki Disease ◽  
Promoter Methylation ◽  
Systemic Vasculitis ◽  
Methylation Status ◽  
Cpg Islands ◽  
Gene Promoter ◽  
Ivig Therapy ◽  
Ivig Treatment ◽  
Fc Fragment ◽  
Cpg Sites

Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause and the Fc Fragment of IgG, Low Affinity IIa, Receptor ( FCGR2A ) gene was reported to involve in increasing susceptibility of KD. Because DNA methylation is one of the epigenetic mechanisms that control gene expression, we hypothesized that methylation status of CpG islands in FCGR2A promoter predisposes an individual to Kawasaki disease. We recruited 36 KD patients and 24 healthy subjects with informed consents. And eleven potential methylation loci within the targeted promoter region (chr1:161474603-161475102) of Fc Fragment of IgG, Low Affinity IIa, Receptor were selected for investigation. Methylation at the CpG sites G, H and J displayed a strongly associations with KD, whereas CpG sites B,C,E,F,H,J and K were found to be correlated with non-responsive to IVIG treatment. In addition, CpG sites G, J and K were predicted as the significant transcription factor binding site for NF-kB, Myc-Max and SP2 respectively. Our study reports a significant association between the promoter methylation of FCGR2A , susceptibility of Kawasaki disease and therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter may be an important marker for optimizing IVIG therapy.

scholarly journals Defects at the Posttranscriptional Level Account for the Low TCRζ Chain Expression Detected in Gastric Cancer Independently of Caspase-3 Activity

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Ana Aguinaga-Barrilero ◽  
Patricia Castro-Sánchez ◽  
Ignacio Juárez ◽  
Alberto Gutiérrez-Calvo ◽  
Noelia Rodríguez-Pérez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Caspase 3 ◽  
Mrna Levels ◽  
Cdna Sequencing ◽  
Control Subjects ◽  
Inflammatory Conditions ◽  
Cell Extracts ◽  
And Control ◽  
Posttranscriptional Level

Background. Reduced TCRζ chain surface has been reported in T cells from patients with different inflammatory conditions and cancer. However, the causes of this diminished expression in cancer remain elusive. Methods. T cell-enriched populations of blood or tissue (tumoral and nontumoral) origin from 44 patients with gastric adenocarcinoma and 33 healthy subjects were obtained. Samples were subjected to cytofluorimetry, Western blot analysis, TCRζ cDNA sequencing experiments, measurement of TCRζ mRNA levels, and caspase-3 activity assays. Results. Cytofluorimetry revealed a decreased TCRζ expression in T cells of patients, assessed either as percentage of cells expressing this chain (blood: control subjects 99.8 ± 0.1 % , patients 98.8 ± 1.1 % P < 0.001 ; tissue: control subjects 96.7 ± 0.9 % , patients tumoral tissue 67.9 ± 27.0 % , patients nontumoral tissue 82.8 ± 12.6 % , P = 0.019 ) or mean fluorescence intensity (MFI) value (blood: control subjects 102.2 ± 26.0 ; patients 58.0 ± 12.3 , P = 0.001 ; tissue: control subjects 99.4 ± 21.4 ; patients tumoral tissue 41.6 ± 21.4 ; patients nontumoral tissue 62.3 ± 16.6 , P = 0.001 ). Other chains pertaining to the TCR-CD3 complex (CD3ε) showed no significant differences (MFI values). Subsequent TCRζ cDNA sequencing experiments or measurements of TCRζ mRNA levels disclosed no differences between patients and control subjects. Evaluation of caspase-3 activity showed higher levels in T cell extracts of patients, and this activity could be decreased by 70% with the use of the inhibitor Ac-DEVD-FMK, although CD3ζ expression levels did not recover. Conclusions. These results further place the defect responsible for the low TCRζ expression in cancer at the posttranscriptional level and suggests contrary to what has been proposed in other pathologies that elevated caspase-3 activity is not the causative agent.

scholarly journals Case report on kawasaki patient with immunoglobulin non-response successfully treated by infliximab

2018 ◽  
Vol 2 (5) ◽  
Author(s):  
Dang Thi Hai Van ◽  
Phan Thi Thuy Ngan ◽  
Do Minh Thuy ◽  
Cao Viet Tung
Keyword(s):  
Case Report ◽  
Kawasaki Disease ◽  
Coronary Arteries ◽  
Systemic Vasculitis ◽  
Treatment Recommendations ◽  
Ivig Treatment ◽  
Inflammation Mediators ◽  
The Past ◽  
Increasing Knowledge

Background: Kawasaki disease KD is self-limiting acute multi-systemic vasculitis of unknown etiology.Current treatment recommendations for acute KD include IVIG and aspirin, but there are no evidence-basedguidelines for children who do not respond to IVIG treatment. Over the past few years, increasing knowledge ofthe pathophysiology of KD has resulted in the identification of key inflammation mediators and the use ofbiologic pathway targeting agents such as TNF and IL-1 inhibitors for children with IVIG-resistant disease.Case presentation: A 11-month-old girl was diagnosed with typical KD and treated with 3 IVIG and 1corticoid therapy, but the coronary arteries continued to dilate. After that, the patient was treated successfullywith Infliximab.

scholarly journals FCGR2APromoter Methylation and Risks for Intravenous Immunoglobulin Treatment Responses in Kawasaki Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Ho-Chang Kuo ◽  
Yu-Wen Hsu ◽  
Mei-Shin Wu ◽  
Peng Yeong Woon ◽  
Henry Sung-Ching Wong ◽  
...  
Keyword(s):  
Kawasaki Disease ◽  
Systemic Vasculitis ◽  
Methylation Status ◽  
Cpg Islands ◽  
Gene Promoter ◽  
Ivig Therapy ◽  
Ivig Treatment ◽  
Cpg Sites ◽  
Therapeutic Outcomes ◽  
Immunoglobulin Gamma

Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause. The low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) gene was reported to be involved in the susceptibility of KD. DNA methylation is one of the epigenetic mechanisms that control gene expression; thus, we hypothesized that methylation status of CpG islands inFCGR2Apromoter associates with the susceptibility and therapeutic outcomes of Kawasaki disease. In this study, 36 KD patients and 24 healthy subjects from out-patient clinic were recruited. Eleven potential methylation sites within the targeted promoter region ofFCGR2Awere selected for investigation. We marked the eleven methylation sites from A to K. Our results indicated that methylation at the CpG sites G, H, and J associated with the risk of KD. CpG sites B, C, E, F, H, J, and K were found to associate with the outcomes of IVIG treatment. In addition, CpG sites G, J, and K were predicted as transcription factors binding sites for NF-kB, Myc-Max, and SP2, respectively. Our study reported a significant association among the promoter methylation ofFCGR2A, susceptibility of KD, and the therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites ofFCGR2Agene promoter should be an important marker for optimizing IVIG therapy.

scholarly journals The Caspase-1/IL-18 Axis of the Inflammasome in Tumor Cells: A Modulator of the Th1/Tc1 Response of Tumor-Infiltrating T Lymphocytes in Colorectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 189
Author(s):  
Linda Bilonda Mutala ◽  
Cécile Deleine ◽  
Matilde Karakachoff ◽  
Delphine Dansette ◽  
Kathleen Ducoin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Lymphocytes ◽  
Tumor Cells ◽  
Ex Vivo ◽  
Explant Culture ◽  
T Cell Response ◽  
Mrna Levels ◽  
Innate And Adaptive Immunity ◽  
Caspase 1 ◽  
Culture Model

In colorectal cancer (CRC), a high density of T lymphocytes represents a strong prognostic marker in subtypes of CRC. Optimized immunotherapy strategies to boost this T-cell response are still needed. A good candidate is the inflammasome pathway, an emerging player in cancer immunology that bridges innate and adaptive immunity. Its effector protein caspase-1 matures IL-18 that can promote a T-helper/cytotoxic (Th1/Tc1) response. It is still unknown whether tumor cells from CRC possess a functional caspase-1/IL-18 axis that could modulate the Th1/Tc1 response. We used two independent cohorts of CRC patients to assess IL-18 and caspase-1 expression by tumor cells in relation to the density of TILs and the microsatellite status of CRC. Functional and multiparametric approaches at the protein and mRNA levels were performed on an ex vivo CRC explant culture model. We show that, in the majority of CRCs, tumor cells display an activated and functional caspase-1/IL-18 axis that contributes to drive a Th1/Tc1 response elicited by TILs expressing IL-18Rα. Furthermore, unsupervised clustering identified three clusters of CRCs according to the caspase-1/IL-18/TIL density/interferon gamma (IFNγ) axis and microsatellite status. Together, our results strongly suggest that targeting the caspase-1/IL-18 axis can improve the anti-tumor immune response in subgroups of CRC.

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