The transcriptomic profile of Kawasaki Disease in humans and mice

Kawasaki Disease (KD) is an illness characterized by severe inflammation in the blood vessels and primarily affects young children (<5 years). Although KD is treatable, the etiology and pathogenesis of the disease remain largely unknown. To accurately characterize the transcriptomic profile and validate animal models for KD, a meta-analysis was carried out among pre-existing RNA sequencing (RNA-seq) data of humans and animals with KD. All deposited RNA-seq data on KD were retrieved from Gene Expression Omnibus (GEO). The sources of RNA were blood and coronary arteries in humans and aortas in control and KD mice induced by Lactobacillus casei cell wall extract. After quality control procedures, differential gene expression profiles were compared between the KD and control groups using fisher’s exact test. The significant genes identified in mice were converted to their human homologs and overlapped with differentially expressed genes in human coronary aortas. Biological pathway analysis was performed on the intersection gene set between humans and mice. In humans, two studies (GEO accession: GSE178491 and GSE64486) revealed 400 genes significantly differentially expressed between control and KD whole blood samples, and 413 genes in control and KD coronary aorta samples. Nevertheless, only 16 genes were differentially expressed in both tissue types from KD patients after adjusting for false discovery rate. In mice, GSE141072 was used for the meta-analysis while stratifying for sex. The expression of 101 genes were significantly altered in KD female mice and 701 genes in KD male mice, both compared to their control counterparts. The differential gene expression profile was similar across sexes in mice, given that over 90% of significant genes found in females were also significant in males (91 out of 101), mostly with consistent directions of regulation. 81 genes overlapped in human and mice data, and 69 out of 81 genes were collaboratively up- or down-regulated in both humans and mice: 30 genes up-regulated and 39 down-regulated. Those include previously identified KD significant genes: CD74, SFRP4, ITGA4, IKZF1, and SERPINA3. Biological pathway analysis on the overlapped gene set highlighted the role of CS, ACO2, OGDH, and DLAT in the regulation of metabolic pathways. In addition, the regulation of the cardiomyopathy pathway represented by DES, TNNC1, TNNI3, MYL3, ADCY5, ATP2A2, ITGA4, and ITGA8 was differentiated between control subjects and their KD counterparts. In conclusion, the meta-analysis using GEO-based RNA-seq data on KD substantiates the similarities in gene expression profiles between humans and mice. Furthermore, KD-induced changes in metabolic and cardiomyopathy pathways are evidently comparable in humans and mice. It is crucial to identify whether the significant genes in diseased mouse models are applicable to humans. Therefore, our study will help develop preventative measures and treatments for children with KD more efficiently. This project is funded by NIH R01HL142214 and DOD W81XWH2110472. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.