Session Title: Genetics and Genomics of Rheumatic Disease II
Session Type: Abstract Submissions (ACR)
Background/Purpose: Kawasaki Disease (KD) is a self-limited vasculitis of unknown etiology that predominantly affects children younger than 5 years. The inflammation associated with KD affects the arterial wall and leads to coronary artery aneurysms (CAA) in 25% of untreated KD children, making KD the most common cause of acquired heart disease in children in developed countries. Genetic predispositions are thought to influence the risk of aneurysm formation, and several gene expression profiling studies for KD were performed to describe KD-specific signatures. However, the lack of power due to limited sample size precluded definitive identification of transcriptomic signatures specific to KD. In this study, we aim to identify the gene expression signatures associated with acute KD by investigating the global gene expression profiles in large number of samples collected in paired-blood samples from acute and convalescent phases. We also investigated the transcript abundance in patients with different IVIG treatment status and different CAA outcomes.
Methods: Illumina gene expression microarray was used to characterize gene expression profiles of 171 KD patients with paired blood samples from the acute and convalescent phase of KD. Quantitative RT-PCR was used to validate the findings of the microarray. A detailed clinical and hematological data was also collected for all the patients. A generalized linear model was used to indentify differentially abundant transcripts between acute and convalescent samples, as well as between IVIG response status and CAA outcomes.
Results: Our data suggest that the complement and coagulation cascades, Toll-like receptor signaling and innate immune related responses were the most prominent pathways that were up-regulated in acute KD patients, while CD8 T cell receptor pathway such was less abundant in acute patients. Toll-like receptors (TLR2, 5 and 8), FCGR1 (A and B), FCRG2 (A and B), CD3, CD4, CD8 and CD28 were amongst the most significant transcripts. We also observed and validated 24 transcripts that were differentially expressed between IVIG responsive and IVIG-resistant KD patients which could play a pivotal role in the disease pathogenesis. These include LILRA5, IL18R1, IRAK3, SORT1 and BMX.
Conclusion: We proposed the potential genetic signatures of acute KD and signatures of IVIG treatment outcomes. The functions of these markers will be further discussed.
L. T. Hoang,
C. C. Khor,
A. N. Mohamed Naim,
M. L. Hibberd,
J. C. Burns,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/global-gene-expression-profiles-reveal-genetic-signatures-of-kawasaki-disease-and-disease-outcome/