Assessment of Risk Factors for Korean Children with Kawasaki Disease

Abstract

Kawasaki disease (KD) is the most common cause of acquired heart disease in children. Intravenous immunoglobulin (IVIG) is the standard therapy for KD, but more than 10% of KD patients do not respond to IVIG and are at high risk for the development of coronary artery lesions (CALs). To identify clinical and genetic risk factors associated with CAL development and IVIG nonresponsiveness, this study analyzed the clinical data for 478 Korean KD patients. Multivariate logistic regression analysis showed that incomplete KD, IVIG nonresponse, fever duration of 7 days or longer, and the CC/AC genotypes of the rs7604693 single nucleotide polymorphism (SNP) in the PELI1 gene were significantly associated with the development of CALs, with odds ratios (ORs) ranging from 2.06 to 3.04. The risk of CAL formation was synergistically increased by the addition of individual risk factors, particularly the genetic variant in the PELI1 gene. Multivariate analysis also showed that a serum albumin level of 3.6 g/dl or lower was significantly associated with nonresponsiveness to IVIG [OR, 2.76; 95% confidence interval (CI), 1.34-5.68; P = 0.006]. Conclusively, incomplete KD, IVIG nonresponsiveness, long febrile days, and the rs7604693 genetic variant in the PELI1 gene are major risk factors for the development of CALs, whereas low serum albumin concentration is an independent risk factor for IVIG nonresponsiveness.

Changes in clinical and laboratory features of Kawasaki disease noted over time in Daejeon, Korea

“…It has been reported that higher CRP, higher maximum platelet, lower albumin, or lower hemoglobin values are associated with IVIG-non responsiveness and the risk of CALs [28][29][30][31]. Our laboratory results provided evidence of changing epidemiology in KD in Korea, and this may be the first laboratory-proven study to demonstrate the results.…”

Inflammation-Induced Hepcidin is Associated with the Development of Anemia and Coronary Artery Lesions in Kawasaki Disease

“…However, it is still unknown how long anemia persists in patients with KD. Elevated inflammatory markers and IVIG nonresponsiveness may be associated with the development of CAL in KD [34]. Our study demonstrated that a lower decrease in hepcidin levels after IVIG treatment was associated with the occurrence of CAL and resistance to IVIG treatment.…”

E3 ubiquitin ligases Pellinos as regulators of pattern recognition receptor signaling and immune responses

“…Increased levels of Pellino-1 and Pellino-2 were found in patients with asthma (110), and kidney transplant recipients experiencing acute rejection showed increased Pellino-2 mRNA levels (111), while Pellino-3 expression is downregulated in the colon of patients with Crohn's disease (67). Interestingly, Pellino-1 SNPs have been linked to increased risks of coronary artery lesions in children with Kawasaki disease, a rare form of vasculitis (112,113). Furthermore, patients with diffuse large B-cell lymphomas showed a close correlation between increased expression of Pellino-1, increased levels of BCL6, and poor prognosis (106).…”