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Published on: May 31, 2024
Increased Expression of Pyroptosis in Leukocytes of Patients with Kawasaki Disease
Kuang-Che Kuo1,2, Ya-Ling Yang3, Mao-Hung Lo1,2
1Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.
Insights
This study found increased caspase gene expression in children with Kawasaki disease (KD), which decreased after treatment. Caspase-3 levels may predict IVIG resistance in KD patients.
Area of Science:
- Immunology
- Molecular Biology
- Pediatrics
Background:
- Kawasaki disease (KD) is a pediatric vasculitis potentially leading to coronary artery aneurysms.
- The role of caspases in KD pathogenesis, specifically apoptosis and pyroptosis, remains under-explored.
Purpose of the Study:
- To investigate the expression and methylation patterns of caspases in KD patients.
- To explore the association between caspase expression and response to intravenous immunoglobulin (IVIG) treatment.
Main Methods:
- Gene expression and methylation analysis using Affymetrix and Illumina platforms on samples from KD patients and controls.
- Validation of findings using real-time quantitative PCR in a separate cohort.
Main Results:
- Significantly elevated mRNA levels of caspase-1, -3, -4, and -5 in KD patients compared to controls.
- Decreased caspase expression post-IVIG treatment.
- Opposite methylation trends for caspase-4 and -5 genes in KD patients versus controls.
- Lower caspase-3 expression in non-responders to IVIG.
Conclusions:
- First report of pyroptotic caspase-1, -4, and -5 upregulation in KD peripheral leukocytes.
- Caspase-3 expression may serve as a biomarker for IVIG resistance in 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 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.
