SummaryAlthough Kawasaki disease (KD) is characterized by a marked activation of the immune system with elevations of serum proinflammatory cytokines and chemokines at acute phase, the major sources for these chemical mediators remain controversial. We analysed the activation status of peripheral blood mononuclear cells (PBMCs) by flow cytometry, DNA microarray and quantitative reverse transcription-polymerase chain reaction. The proportions of CD69 + cells in both natural killer cells and gdT cells at acute-phase KD were significantly higher than those at convalescent-phase KD. Microarray analysis revealed that five genes such as NAIP, IPAF, S100A9, FCGR1A and GCA up-regulated in acute-phase KD and the pathways involved in acute phase KD were related closely to the innate immune system. The relative expression levels of damage-associated molecular pattern molecule (DAMP) (S100A9 and S100A12) genes in PBMCs at acute-phase KD were significantly higher than those at convalescent-phase KD, while those of TNFA, IL1B and IL6 genes were not significantly different between KD patients and healthy controls. Intracellular production of tumour necrosis factor-a, interlaukin-10 and interferon-g in PBMCs was not observed in KD patients. The present data have indicated that PBMCs showed a unique activation status with high expression of DAMP genes but low expression of proinflammatory cytokine genes, and that the innate immune system appears to play a role in the pathogenesis and pathophysiology of KD.

This study aimed to assess the outcome of cardiovascular diseases for patients with chronic active Epstein-Barr virus infection (CAEBV). The study enrolled 15 patients (7 boys and 8 girls) who fulfilled the diagnostic criteria for CAEBV, including 10 patients with T-cell type and 3 patients with natural killer (NK)-cell type. The median age at the CAEBV onset was 6.3 years (range, 1.2-17.8 years). Regular cardiologic studies were performed during the median follow-up period of 8 years (range, 2-20 years). Nine patients (60%) had cardiac diseases including coronary artery lesion (CAL) (n = 4, 44%), decreased left ventricular ejection fraction and pericardial effusion in (n = 3, 33%), complete atrioventricular block (n = 1), and sudden arrest (n = 1). The frequency of fever (78%, p = 0.04) or cytopenias (100%, p = 0.01), as the major symptom among patients with cardiac complications, was higher than among those without complications. The median time from disease onset to detection of CAL was 3.4 years (range, 1.8-8.6 years). The mean z-score increased to 3.98. Seven patients (78%) with cardiac complications died of disease progression, hematopoietic stem cell transplantation-related events, or both. In two patients, CAL regressed after allogeneic cord blood transplantation. Among CAEBV patients, CAL was the most common cardiac complication and could not be controlled without the eradication of EBV-infected T- and NK-cells.

Kawasaki disease (KD) is an acute febrile disorder characterized by systemic vasculitis primarily occurring in coronary arteries. Matrix metalloproteinases (MMPs) have been considered to play pathophysiologic roles in the development of coronary artery lesions (CALs); therefore, an evaluation of the genetic contributions of the MMP genes to the development of CALs in KD patients would be beneficial for the prediction of CAL formation. We focused on the known functional single nucleotide polymorphisms (SNPs) in the MMP genes (MMP-2-735CϾT, MMP-3-1612 5A/6A, MMP-9-1562CϾT, and performed the association study between these SNPs and CAL formation in KD. The study population consisted of 44 KD patients with CALs and 92 without CALs and 175 healthy controls. As a result, allele and genotype frequencies of MMP-13-77AϾG showed significant differences between KD patients with CALs and without CALs (p ϭ 0.00989 and p ϭ 0.00551, respectively). The estimated frequencies of the G-C haplotype in the MMP-13 gene promoter were significantly lower in KD patients with CALs than in those without CALs. There was no association between other MMP genes and CAL formation. In conclusion, the genetic evaluation by association study demonstrated that the MMP-13 gene, at least in part, contributed to the development of CALs in KD. K awasaki disease (KD) is an acute febrile disorder characterized by systemic vasculitis predominantly occurring in infants and young children. Although the administration of i.v. immunoglobulin (IVIG) in the acute phase of the disease significantly reduces the development of coronary artery lesions (CALs), 2%-15% of KD patients still suffer from this complication (1,2). There is a strong inflammatory predilection for the coronary arteries, and the inflammation in subendothelial layers includes striking edema and infiltration of CD8ϩ T cells, monocytes, and macrophages with little or no fibrinoid necrosis and few polymorphonuclear cells (3). Inflammatory cells infiltrating from the lumen and from the adventitia to the media appear to mediate transmural damage to the arteries, followed by the development of coronary aneurysms.The inability to obtain affected coronary arteries has precluded a comprehensive understanding of the mechanism how the pathologic changes in the vessel wall evolve. As a substitute for pathologic evaluation of the affected tissues, the measurements of cytokines in serum and gene expression levels in peripheral blood cells were studied for the prediction of CAL formation (4). In previous studies, serum vascular endothelial growth factor (VEGF) and hepatocyte growth factor levels in patients with KD were remarkably high in the acute phase and were major risk factors for the occurrence of CALs, probably by an increasing permeability in vessels to cause vascular edema (4 -6). A significant elevation of serum matrix metalloproteinase (MMP)-9 levels and a remarkably high expression of the MMP-9 mRNA in the leukocytes were detected during the acute phase of KD (7), suggesting that MMP-9...

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ObjectiveEpidemics of Kawasaki disease (KD) are well known; however, the seasonal variation in the clinical course of KD is uncertain. The aim of this study was to investigate the seasonality in the clinical course of KD.MethodsThis study included 744 patients who were admitted to six hospitals in Kitakyushu City for KD from 2010 to 2014. We divided the patients into two groups according to the average monthly temperature (warm and cold periods) and compared the clinical courses of KD.ResultsThe clinical courses of 715 patients who were initially treated with intravenous immunoglobulin (IVIG) were investigated. The proportion of patients with resistance to the initial IVIG therapy was significantly higher during the warm period than during the cold period (p=0.016). There was no seasonality in the proportion of patients with coronary artery abnormalities.ConclusionSeasonality was observed in the response to IVIG therapy of patients with KD.