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Serum Levels of Syndecan-1 in Patients With Kawasaki Disease.

ABSTRACT: BACKGROUND:Kawasaki disease (KD) is an acute systemic vasculitis with coronary artery lesions (CALs) being the major concern. Syndecan-1 (SDC-1) is a major core protein expressed on the glycocalyx of endothelial cells. Shed SDC-1 in serum is regarded as a biomarker for endothelial activation or damage. METHODS:In this study, we aimed to determine the serum levels of SDC-1 and evaluate the relationship between serum levels of SDC-1 and the CALs in the acute phase of KD. Serum SDC-1 levels were measured in 119 children with KD and in 43 healthy children as normal controls and in 40 children with febrile disease. All KD patients were administrated a single dose of intravenous immunoglobulin and aspirin per os within 10 days of KD onset. RESULTS:Serum levels of SDC-1, in addition to albumin and hemoglobin, were significantly increased in patients with KD than in healthy controls and febrile controls. Furthermore, the serum levels of SDC-1, albumin and hemoglobin were significantly elevated in KD patients with CALs than those without CALs. Additionally, serum levels of SDC-1 were significantly correlated with levels of hemoglobin and serum albumin in patients with KD. After intravenous immunoglobulin therapy, serum levels of interleukin-6, soluble cell adhesion molecules-1 and resistin were reduced while serum levels of SDC-1 were significantly increased in KD patients. CONCLUSIONS:SDC-1 serum levels may mirror vascular endothelial damage and inflammation in KD. This might be utilized as a potential novel target for coronary artery protection in KD patients.

SUBMITTER: Luo L

PROVIDER: S-EPMC6296840 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Serum Levels of Syndecan-1 in Patients With Kawasaki Disease.

Luo Li L Feng Siqi S Wu Yao Y Su Ya Y Jing Fengchuan F Yi Qijian Q

The Pediatric infectious disease journal 20190101 1

<h4>Background</h4>Kawasaki disease (KD) is an acute systemic vasculitis with coronary artery lesions (CALs) being the major concern. Syndecan-1 (SDC-1) is a major core protein expressed on the glycocalyx of endothelial cells. Shed SDC-1 in serum is regarded as a biomarker for endothelial activation or damage.<h4>Methods</h4>In this study, we aimed to determine the serum levels of SDC-1 and evaluate the relationship between serum levels of SDC-1 and the CALs in the acute phase of KD. Serum SDC-1 ...[more]

PMID: 29601451

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Project description:BackgroundResistance to intravenous immunoglobulin (IVIG) occurs in 10-20% of patients with Kawasaki disease (KD). The risk of resistance is about two-fold higher in patients with elevated gamma glutamyl transferase (GGT) levels. We sought to understand the biological mechanisms underlying IVIG resistance in patients with elevated GGT levels.MethodWe explored the association between elevated GGT levels and IVIG-resistance with a cohort of 686 KD patients (Cohort I). Gene expression data from 130 children with acute KD (Cohort II) were analyzed using the R square statistic and false discovery analysis to identify genes that were differentially represented in patients with elevated GGT levels with regard to IVIG responsiveness. Two additional KD cohorts (Cohort III and IV) were used to test the hypothesis that sialylation and GGT may be involved in IVIG resistance through neutrophil apoptosis.ResultsThirty-six genes were identified that significantly explained the variations of both GGT levels and IVIG responsiveness in KD patients. After Bonferroni correction, significant associations with IVIG resistance persisted for 12 out of 36 genes among patients with elevated GGT levels and none among patients with normal GGT levels. With the discovery of ST6GALNAC3, a sialyltransferase, as the most differentially expressed gene, we hypothesized that sialylation and GGT are involved in IVIG resistance through neutrophil apoptosis. We then confirmed that in Cohort III and IV there was significantly less reduction in neutrophil count in IVIG non-responders.ConclusionsGene expression analyses combining molecular and clinical datasets support the hypotheses that: (1) neutrophil apoptosis induced by IVIG may be a mechanism of action of IVIG in KD; (2) changes in sialylation and GGT level in KD patients may contribute synergistically to IVIG resistance through blocking IVIG-induced neutrophil apoptosis. These findings have implications for understanding the mechanism of action in IVIG resistance, and possibly for development of novel therapeutics.

Dataset Information

Serum Levels of Syndecan-1 in Patients With Kawasaki Disease.

Publications

Serum Levels of Syndecan-1 in Patients With Kawasaki Disease.

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