Objective. To investigate the roles of serum Th1 and Th2 cytokines in Kawasaki disease (KD) and determine whether the Th1/Th2 cytokine profiles in children with KD may be involved in intravenous immunoglobulin (IVIG) resistance and development of coronary artery lesions (CALs).Methods. Serum Th1 and Th2 cytokines, including interferon-␥ (IFN␥), tumor necrosis factor ␣ (TNF␣), interleukin-10 (IL-10), IL-6, IL-4, and IL-2, were measured using a cytometric bead array in the serum of 143 patients with KD before and after treatment with IVIG (pre-IVIG, at 3 days after temperature normalization following IVIG treatment [post-IVIG], and 1 month posttreatment).Results. Levels of IL-6, IL-10, TNF␣, and IFN␥ were significantly increased in KD patients pre-IVIG. Post-IVIG, the levels of IL-6, IL-10, and IFN␥ quickly decreased. The levels of TNF␣ decreased significantly after IVIG treatment in KD patients without CALs post-IVIG and in KD patients who were IVIG responders, but increased slightly in KD patients with CALs post-IVIG and in KD patients who were IVIG nonresponders. Before IVIG treatment, the levels of IL-4, IL-6, IL-10, and IFN␥ were significantly higher in KD patients with CALs than in those without CALs. The post-IVIG levels of IL-6 and IL-10 were significantly higher in IVIG nonresponders than in IVIG responders. Pre-IVIG, an IL-10 level >8 pg/ml had a sensitivity of 75.0% and a specificity of 64.4% for predicting CALs, while a TNF␣ level <2 pg/ml had a sensitivity of 66.7% and a specificity of 74.2% for predicting IVIG resistance. Post-IVIG, an IL-6 level >10 pg/ml had a sensitivity of 67.9% and a specificity of 81.7% for predicting CALs, while an IL-10 level >6 pg/ml had a sensitivity of 53.6% and a specificity of 86% for predicting CALs.Conclusion. Determination of the serum Th1/Th2 cytokine profile may be helpful for predicting the disease prognosis and targeting treatment strategies in patients with KD.

Genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) associated with Kawasaki disease (KD). In this study, we replicated the associations of 10 GWAS-identified SNPs with KD in a Han Chinese population. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression, and cumulative effect of non-risk genotypes were also performed. Although none of the SNPs reached the corrected significance level, 4 SNPs showed nominal associations with KD risk. Compared with their respective wild type counterparts, rs1801274 AG+GG genotypes and rs3818298 TC+CC genotypes were nominally associated with the reduced risk of KD (OR = 0.77, 95% CI = 0.59–0.99, P = 0.045; OR = 0.74, 95% CI = 0.56–0.98, P = 0.038). Meanwhile, rs1801274 GG genotype, rs2736340 CC genotype or rs4813003 TT genotype showed a reduced risk trend (OR = 0.57, 95% CI = 0.35–0.93, P = 0.024; OR = 0.46, 95% CI = 0.26–0.83, P = 0.010; OR = 0.64, 95% CI = 0.43–0.94, P = 0.022), compared with rs1801274 AG+AA genotypes, rs2736340 CT+TT genotypes or rs4813003 TC+CC genotypes, respectively. Furthermore, a cumulative effect was observed with the ORs being gradually decreased with the increasing accumulative number of non-risk genotypes (Ptrend<0.001). In conclusion, our study suggests that 4 GWAS-identified SNPs, rs2736340, rs4813003, rs3818298 and rs1801274, were nominally associated with KD risk in a Han Chinese population individually and jointly.

Ca2+/nuclear factor of activated T-cells (Ca2+/NFAT) signaling pathway may play a crucial role in Kawasaki disease (KD). We investigated 16 genetic variants, selected by bioinformatics analyses or previous studies, in 7 key genes involved in this pathway in a Chinese population. We observed a significantly or marginally increased KD risk associated with rs2720378 GC + CC genotypes (OR = 1.39, 95% CI = 1.07–1.80, P = 0.014) or rs2069762 AC + CC genotypes (OR = 1.28, 95% CI = 0.98–1.67, P = 0.066), compared with their wild type counterparts. In classification and regression tree analysis, individuals carrying the combined genotypes of rs2720378 GC or CC genotype, rs2069762 CA or CC genotype and rs1561876 AA genotype exhibited the highest KD risk (OR = 2.12, 95% CI = 1.46–3.07, P < 0.001), compared with the lowest risk carriers of rs2720378 GG genotype. Moreover, a significant dose effect was observed among these three variants (Ptrend < 0.001). In conclusion, this study implicates that single- and multiple-risk genetic variants in this pathway might contribute to KD susceptibility. Further studies on more comprehensive single nucleotide polymorphisms, different ethnicities and larger sample sizes are warranted, and the exact biological mechanisms need to be further clarified.

ObjectivesRecent genome-wide association study found rs1801274, a functional single nucleotide polymorphism (SNP) in IgG receptor gene FCGR2A, was associated with increased risk of Kawasaki disease (KD). However, subsequent studies on the role of this SNP were limited and controversial.MethodsA case-control study was conducted in a Chinese Han population including 428 KD patients and 493 controls to examine the association between rs1801274 and KD susceptibility. A meta-analysis was performed in combination with the relevant published studies to further clarify such an association.ResultsOur case-control study found that rs1801274 was significantly associated with increased risk of KD in the Chinese Han population, with an odds ratio (OR) of 1.58 (95% CI = 0.96–2.62) for the GA genotype and 1.93 (95% CI = 1.16–3.19) for the AA genotype compared with the GG genotype. The result of meta-analysis further demonstrated that the A allele of rs1801274 was significantly correlated with KD risk under the allelic model (OR = 1.35, 95% CI = 1.27–1.44) without heterogeneity by fixed-effects model analysis (Q = 17.30, p = 0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis.ConclusionThese results further confirm that rs1801274 in the FCGR2A gene is significantly associated with increased risk of KD.

IntroductionKawasaki disease (KD), an acute febrile disease, characterized by systemic vasculitis, predominantly affects infants and children under 5 years of age. Coronary artery lesions (CALs) are its most critical complication, and the etiology remains unknown yet. In order to explore the value of resistin, S100A12 and soluble receptor for advanced glycation end products (sRAGE) in the pathophysiology of KD, we studied the serum levels of resistin, S100A12 and sRAGE in different stages of KD.MethodsSerum levels of resistin, S100A12 and sRAGE were measured by enzyme-linked immunosorbent assay (ELISA) method in 15 healthy children and 40 KD patients at acute, afebrile and subacute stage.ResultsThe resistin and S100A12 levels, including the ratio of resistin to sRAGE and S100A12 to sRAGE increased significantly in the acute stage, and decreased progressively in the afebrile and subacute stage. However, the sRAGE levels decreased significantly in the acute stage, and increased progressively in the afebrile and subacute stage. In the acute, afebrile and subacute stage, the resistin levels were higher in intravenous immunoglobulin (IVIG) non-responders (0.64 ± 0.30, 0.48 ± 0.35, 0.28 ± 0.19, × 102 ng/ml) than in IVIG responders (0.35 ± 0.24, 0.21 ± 0.19, 0.12 ± 0.05, × 102 ng/ml). In the acute and subacute stage, the S100A12 levels were higher in IVIG non-responders (7.92 ± 2.61, 4.98 ± 4.75, × 102 ng/ml) than in IVIG responders (5.05 ± 3.22, 2.35 ± 2.26, × 102 ng/ml). In the afebrile and subacute stage, the sRAGE levels were lower in IVIG non-responders (3.51 ± 2.64, 3.65 ± 3.27, × 102 pg/ml) than in IVIG responders (6.00 ± 2.78, 7.19 ± 2.88, × 102 pg/ml). The resistin levels were positively correlated with S100A12 levels. The sRAGE levels were negatively related with S100A12 and resistin levels.ConclusionsResistin, S100A12 and sRAGE are involved in the pathophysiology of KD.