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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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/2075-4418/11/11/2035 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:34:26Z |
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| language | English |
| last_indexed | 2024-03-10T05:34:26Z |
| publishDate | 2021-11-01 |
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| series | Diagnostics |
| spelling | doaj.art-654f1af350ba44bf88c83cb73b930c142023-11-22T23:01:24ZengMDPI AGDiagnostics2075-44182021-11-011111203510.3390/diagnostics11112035Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki DiseaseKuang-Che Kuo0Ya-Ling Yang1Mao-Hung Lo2Xin-Yuan Cai3Mindy Ming-Huey Guo4Ho-Chang Kuo5Ying-Hsien Huang6Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, TaiwanBackground: 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.https://www.mdpi.com/2075-4418/11/11/2035Kawasaki diseasecoronary arterial lesionspyroptosiscaspasesIVIG resistance |
| spellingShingle | 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 Diagnostics Kawasaki disease coronary arterial lesions pyroptosis caspases IVIG resistance |
| title | 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_short | Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease |
| title_sort | increased expression of pyroptosis in leukocytes of patients with kawasaki disease |
| topic | Kawasaki disease coronary arterial lesions pyroptosis caspases IVIG resistance |
| url | https://www.mdpi.com/2075-4418/11/11/2035 |
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