The transcriptional profile of coronary arteritis in Kawasaki disease

Abstract

BackgroundKawasaki Disease (KD) can cause potentially life-threatening coronary arteritis in young children, and has a likely infectious etiology. Transcriptome profiling is a powerful approach to investigate gene expression in diseased tissues. RNA sequencing of KD coronary arteries could elucidate the etiology and the host response, with the potential to improve KD diagnosis and/or treatment.MethodsDeep RNA sequencing was performed on KD (n = 8) and childhood control (n = 7) coronary artery tissues, revealing 1074 differentially expressed mRNAs. Non-human RNA sequences were subjected to a microbial discovery bioinformatics platform, and microbial sequences were analyzed by Metastats for association with KD.ResultsT lymphocyte activation, antigen presentation, immunoglobulin production, and type I interferon response were significantly upregulated in KD arteritis, while the tumor necrosis factor α pathway was not differentially expressed. Transcripts from known infectious agents were not specifically associated with KD coronary arteritis.ConclusionsThe immune transcriptional profile in KD coronary artery tissues has features of an antiviral immune response such as activated cytotoxic T lymphocyte and type I interferon-induced gene upregulation. These results provide new insights into the pathogenesis of KD arteritis that can guide selection of new immunomodulatory therapies for high-risk KD patients, and provide direction for future etiologic studies.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-2323-5) contains supplementary material, which is available to authorized users.

Arterial immune protein expression demonstrates the complexity of immune responses in Kawasaki disease arteritis

“…AIF1, an actin‐binding protein induced by IFN, was expressed highly in a transmural distribution in KD coronary arteries in antigen‐presenting cells. AIF1 was up‐regulated 5·5‐fold in the KD coronary artery transcriptome . We identified diffuse transmural expression of AIF1 protein in all 12 KD coronary artery specimens (Fig.…”

“…CD20, ZBP1 and TLR‐7 proteins were also up‐regulated in KD arteritis. MS4A1 (the gene for CD20), ZBP1 and TLR‐7 were up‐regulated 14·2‐, 5·6‐ and 11·1‐fold, respectively, in the KD coronary artery transcriptome . Significantly increased transmural expression of CD20 was observed in all 12 KD cases compared with control coronary arteries (Fig.…”

“…CD74, a chaperone that associates with major histocompatibility complex (MHC) class II to regulate antigen presentation for immune response, was up‐regulated significantly in the media of KD coronary arteries compared to controls and localizes to macrophages. CD74 was up‐regulated 7·7‐fold in the KD coronary artery transcriptome . CD74 protein was expressed diffusely in both the media and adventitia of all 12 cases, whereas there was no expression of CD74 in the media of any of the 12 control coronary arteries (Fig.…”

“…CD1c, a marker of myeloid DCs, was up‐regulated highly in a transmural pattern in KD coronary arteries. CD1c was up‐regulated 3·9‐fold in the KD coronary artery transcriptome . CD1c was expressed highly in a transmural pattern in 10 of 12 cases.…”

“…). IL‐18 was up‐regulated 3·4‐fold in the KD coronary artery transcriptome . IL‐18 protein was expressed in a transmural pattern in 9 KD cases and in the adventitia in 2 KD cases.…”