Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease

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 t...

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Autores principales: Kuang-Che Kuo, Ya-Ling Yang, Mao-Hung Lo, Xin-Yuan Cai, Mindy Ming-Huey Guo, Ho-Chang Kuo, Ying-Hsien Huang
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:654f1af350ba44bf88c83cb73b930c142021-11-25T17:20:59ZIncreased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease10.3390/diagnostics111120352075-4418https://doaj.org/article/654f1af350ba44bf88c83cb73b930c142021-11-01T00:00:00Zhttps://www.mdpi.com/2075-4418/11/11/2035https://doaj.org/toc/2075-4418Background: 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<sup>®</sup> 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 (<i>p</i> < 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.Kuang-Che KuoYa-Ling YangMao-Hung LoXin-Yuan CaiMindy Ming-Huey GuoHo-Chang KuoYing-Hsien HuangMDPI AGarticleKawasaki diseasecoronary arterial lesionspyroptosiscaspasesIVIG resistanceMedicine (General)R5-920ENDiagnostics, Vol 11, Iss 2035, p 2035 (2021)
institution DOAJ
collection DOAJ
language EN
topic Kawasaki disease
coronary arterial lesions
pyroptosis
caspases
IVIG resistance
Medicine (General)
R5-920
spellingShingle Kawasaki disease
coronary arterial lesions
pyroptosis
caspases
IVIG resistance
Medicine (General)
R5-920
Kuang-Che Kuo
Ya-Ling Yang
Mao-Hung Lo
Xin-Yuan Cai
Mindy Ming-Huey Guo
Ho-Chang Kuo
Ying-Hsien Huang
Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease
description 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<sup>®</sup> 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 (<i>p</i> < 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.
format article
author Kuang-Che Kuo
Ya-Ling Yang
Mao-Hung Lo
Xin-Yuan Cai
Mindy Ming-Huey Guo
Ho-Chang Kuo
Ying-Hsien Huang
author_facet Kuang-Che Kuo
Ya-Ling Yang
Mao-Hung Lo
Xin-Yuan Cai
Mindy Ming-Huey Guo
Ho-Chang Kuo
Ying-Hsien Huang
author_sort Kuang-Che Kuo
title Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease
title_short Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease
title_full Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease
title_fullStr Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease
title_full_unstemmed Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease
title_sort increased expression of pyroptosis in leukocytes of patients with kawasaki disease
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/654f1af350ba44bf88c83cb73b930c14
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