Abstract
BackgroundGlobal gene expression profiling can provide insight into the underlying pathophysiology of disease processes. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. Although the clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD.MethodsTo gain further insight into the molecular mechanisms underlying KD, we investigated the acute and convalescent whole blood transcriptional profiles of 146 KD subjects and compared them with the transcriptional profiles of pediatric patients with confirmed bacterial or viral infection, and with healthy control children. We also investigated the transcript abundance in patients with different intravenous immunoglobulin treatment responses and different coronary artery outcomes.ResultsThe overwhelming signature for acute KD involved signaling pathways of the innate immune system. Comparison with other acute pediatric infections highlighted the importance of pathways involved in cell motility including paxillin, relaxin, actin, integrins, and matrix metalloproteinases. Most importantly, the IL1β pathway was identified as a potential therapeutic target.ConclusionOur study revealed the importance of the IL-1 signaling pathway and a prominent signature of innate immunity and cell migration in the acute phase of the illness.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0102-6) contains supplementary material, which is available to authorized users.
Highlights
Kawasaki disease (KD) is a self-limited vasculitis of unknown etiology that predominantly affects children aged younger than 5 years [1]
Gene ontology analysis Acute vs. convalescent KD Because we had detailed clinical laboratory data from our KD subjects concurrent with the whole blood RNA samples, we assessed whether cell subtype numbers affected gene ontology
Fewer Differentially expressed transcripts (DAT) (1,083 vs. 2,414) were identified when cell numbers were taken into account and gene ontology analysis for the more abundant transcripts at acute stage (819 and 1,541) identified 110 and 183 significant pathways in the Generalized linear model (GLM) and Z test, respectively
Summary
Kawasaki disease (KD) is a self-limited vasculitis of unknown etiology that predominantly affects children aged younger than 5 years [1]. The incidence of the disease varies widely among different populations from a high of 240 in Japan to five in Norway per 100,000 children aged under 5 years [2,3]. The inflammation associated with KD affects the arterial wall and leads to coronary artery aneurysms (CAA) in 25% of untreated KD children [4], making KD the most common cause of acquired heart disease in children in developed countries [5]. Kawasaki disease (KD) is an acute, self-limited vasculitis whose etiology remains unknown. The clinical illness shares certain features with other pediatric infectious diseases, the occurrence of coronary artery aneurysms in 25% of untreated patients is unique to KD
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