Association between serum miR-221-3p and intravenous immunoglobulin resistance in children with Kawasaki disease.

OBJECTIVES: Intravenous immunoglobulin (IVIG) resistance was a major cause of coronary artery lesions in children with Kawasaki disease (KD). However, the cause of IVIG resistance in KD remains unknown. miR-221-3p has been confirmed involved in cardiovascular diseases and rheumatoid arthritis. The purpose of this study was to investigate the association between miR-221-3p and IVIG resistance in children with KD. METHODS: Fifty-five KD patients and 29 healthy controls (HCs) were enrolled in this study. KD patients were divided into group of sensitive to IVIG (IVIG-response, n = 42) and group of resistant to IVIG (IVIG-resistance, n = 13), group of 10 KD patients with coronary artery lesions (CALs, KD-CALs) and group of 10 sex- and age-matched KD patients without CALs (KD-NCALs). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of miR-221-3p. RESULTS: Compared with the HCs group, miR-221-3p were significantly increased in the KD group (p < 0.05), and the IVIG-resistance group had higher levels of miR-221-3p than those in the IVIG-response group (p < 0.05). CRP (C-reactive protein), PCT (procalcitonin), NLR (neutrophil-lymphocyte ratio) were positively correlated with miR-221-3p in KD patients. In addition, the group of IVIG resistance had a higher level of Kobayashi Score (p < 0.001). The receiver operating characteristic curve showed that miR-221-3p had a better value for diagnosis IVIG resistance in children with KD than Kobayashi Score with the AUC of 0.811 (95% CI, 0.672-0.951), 0.793 (95% CI, 0.618-0.968), respectively. Additionally, miR-221-3p was elevated (p < 0.05) and showed an AUC value of 0.83 (95% CI, 0.648-1.000, p < 0.05) for the prediction of the complication of coronary artery abnormalities in the group of KD with CALs. CONCLUSIONS: miR-221-3p might be involved in the pathogenesis of KD and IVIG resistance and miR-221-3p can be used as a new potential biomarker to predict IVIG resistance in children with KD.

The relationship between TNF-like protein 1A and coronary artery aneurysms in children with Kawasaki disease.

Kawasaki disease (KD) is an acute, systemic vasculitis of unknown etiology that occurs predominantly in infants and children, and the most crucial complication of KD is coronary artery aneurysm (CAA). Tumor necrosis factor (TNF)-like protein 1A (TL1A) is a member of the TNF superfamily, which possesses the ability of maintaining vascular homeostasis and regulating immune responses. This study aimed to examine serum TL1A levels in KD patients, and to investigate the relationship between TL1A and CAAs in children with KD. Blood samples were recruited from 119 KD patients, 35 febrile controls (FCs), and 37 healthy controls (HCs). The KD group was further divided into KD with CAAs (KD-CAAs) and KD non-CAAs (KD-NCAAs) groups. Serum TL1A levels were measured using enzyme-linked immunosorbent assays, and clinical parameters were collected from KD patients. Serum TL1A levels of KD patients in the acute phase of KD were significantly higher than in the FC and HC groups. In particular, serum TL1A levels were substantially increased in the KD-CAA group compared with the KD-NCAA group. Furthermore, TL1A levels in the KD group were positively correlated with the duration of fever and the time point of IVIG and WBC levels, but negatively correlated with levels of RBC, Hb and albumin. TL1A might be involved in KD-associated vasculitis and in the development of CAAs.

Association between adropin and coronary artery lesions in children with Kawasaki disease.

Kawasaki disease (KD) is an acute systemic vasculitis in children. Coronary artery lesions (CALs) are the most serious complications in KD, but the pathogenesis is still unclear so far. Adropin, a new biopeptide, plays an important role in metabolism and cardiovascular function. The aim of this study was to explore the relationship between adropin and KD. 66 KD patients and 22 healthy controls (HCs) were included in the study. KD patients were divided into KD with coronary artery lesions (KD-CALs) group and KD without CALs (KD-NCALs) group. The levels of serum adropin were determined by enzyme-linked immunosorbent assay (ELISA). Compared with the HC group, adropin concentrations were significantly increased in the KD group (p < 0.05), and the KD-CAL group had higher levels of adropin than those in the KD-NCAL group (p < 0.05). Pct (Procalcitonin) and DD (D-dimer) were positively correlated with adropin in the KD group (p < 0.05). Moreover, adropin had positive correlations with CRP (C-reactive protein) and DD in the KD-NCAL group and positive correlations with Pct, PLR (platelet-to-lymphocyte ratio), and DD in the KD-CAL group (p < 0.05). The receiver operating characteristic (ROC) curve showed that the best threshold value of serum adropin level was more than 2.8 ng/mL, with 72.2% sensitivity and 71.4% specificity for predicting CALs in children with KD.Conclusion: Adropin might be involved in the pathogenesis of KD and CALs and can be used as an auxiliary diagnostic biomarker of KD. What is Known: • CALs in KD were mainly caused by inflammation, immune imbalance, and vascular endothelial dysfunction, and adropin is involved in metabolic diseases and cardiovascular diseases. What is New: • In this study, we have found the relationship between adropin and KD, and serum adropin level can be used as an auxiliary diagnostic biomarker to predict CALs in KD.

The Relationship between Retinol-Binding Protein 4 and Markers of Inflammation and Thrombogenesis in Children with Kawasaki Disease.

BACKGROUND: Kawasaki disease (KD) is a self-limited vasculitis with unknown etiologies, and coronary artery lesions (CALs) are the most common and serious complications. Retinol-binding protein 4 (RBP4) has been confirmed effects on vasodilation, platelet activation inhibition, and cardiovascular diseases by researches. Therefore, this study was aimed at investigating the relationship between RBP4 and inflammation as well as thrombogenesis in children with KD. METHODS: 79 subjects were from 62 children with KD and 17 healthy controls (HCs). The KD group was divided into KD with CALs (KD-CALs) and KD without CALs (KD-NCALs), and the serum RBP4 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared with the HC group, serum RBP4 levels in the KD group were significantly decreased (p < 0.05). RBP4, hemoglobin (Hb), and mean platelet volume (MPV) levels were higher, while platelet counts (Plt) and thrombin time (TT) levels were lower in the KD-NCALs group than in the KD-CALs group (p < 0.05). RBP4 had positive correlation with time point of intravenous immunoglobulin (IVIG), Hb, and percentage of leukomonocytes (L%) and negative correlation with the percentage of neutrophils (N%), MPV, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), prothrombin time (PT), fibrinogen (Fbg), and D-dimer (DD) in the KD group; RBP4 had positive correlation with the time point of IVIG and L% and negative correlation with N%, MPV, and NLR in the KD-NCALs group; and RBP4 had positive correlation with Hb and L% and negative correlation with N%, CRP, NLR, and PT in the KD-CALs group (p < 0.05). Multiple linear regression analysis confirmed that Hb and CRP in the KD group, MPV and N% in the KD-NCALs group, and PT and CRP in the KD-CALs group were independent predictors of RBP4 (p < 0.05). CONCLUSION: Lower RBP4 was observed in the KD group than in the HC group, and RBP4 had associations with markers of inflammation and thrombogenesis in children with KD.

Decreased serum Annexin A1 levels in Kawasaki disease with coronary artery aneurysm.

BACKGROUND: Kawasaki disease (KD) is an acute and systemic vasculitis whose etiology remains unclear. The most crucial complication is the formation of coronary artery aneurysm (CAA). Annexin A1 (ANXA1) is an endogenous anti-inflammatory agent and pro-resolving mediator involved in inflammation-related diseases. This study sought to investigate the serum ANXA1 levels in KD patients and further explore the relationship between ANXA1 and CAA, as well as additional clinical parameters. METHODS: Serum samples were collected from 95 KD patients and 39 healthy controls (HCs). KD patients were further divided into two groups: KD with CAAs (KD-CAAs) and KD non-CAAs (KD-NCAAs). Serum levels of ANXA1 and interleukin-6 (IL-6) were determined using enzyme-linked immunosorbent assays. RESULTS: Serum ANXA1 levels in the KD group were significantly lower than in the HC group. In particular, serum ANXA1 levels were substantially lower in the KD-CAA groups. Moreover, serum ANXA1 levels were positively correlated with N%, C-reactive protein (CRP), and IL-6 but negatively correlated with L% in the KD group. Positive correlations between serum ANXA1 levels and erythrocyte sedimentation rate (ESR), IL-6, and D-dimer (DD) were observed in the KD-CAA group. CONCLUSIONS: ANXA1 may be involved in the development of KD, and downregulation of ANXA1 may lead to the hypercoagulability seen in KD. IMPACT: For the first time, it was demonstrated that serum ANXA1 levels were significantly decreased in Kawasaki disease with coronary artery aneurysms. ANXA1 might be involved in the acute phase of Kawasaki disease. Low serum concentrations of ANXA1 might lead to the hypercoagulability stage in Kawasaki disease. ANXA1 might be a potential therapeutic target for patients with Kawasaki disease.

Hypomethylation of C1q/tumor necrosis factor-related protein-1 promoter region in whole blood and risks for coronary artery aneurysms in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is characterized as a self-limited systemic vasculitis. C1q/tumor necrosis factor-related protein-1 (CTRP1) had been associated with the occurrence of vasculitis in KD. Methylation at the promoter region of certain genes was reported to be involved in the development process of KD. This study aims to investigate the methylation levels of CTRP1 in KD, as well as, its potential to predict coronary artery aneurysms (CAAs). METHODS: 31 patients with KD and 14 healthy controls (HCs) were recruited into this study. The KD group was further divided into KD with CAA (KD-CAAs) group and KD without NCAAs (KD-NCAAs) group. Methylation levels of CpG sites were determined by MethylTarget sequencing, a method that uses multiple targeted CpG methylation analysis. RESULTS: The methylation levels of CTRP1 promoter region in the KD group were lower than that in the HC group at all predicted CpG sites, especially at sites 34, 51, 69, 79, 176 and 206. Compared with KD-CAAs group, the methylation levels of almost every CpG sites of CTRP1 were increased in the KD-NCAAs group, with site 69 and 154 found to be strongly related to the occurrence of CAAs. CONCLUSIONS: The difference in methylation levels of CTRP1 promoter may be involved in the development process of KD, and may be a potential predictive marker for the occurrence of CAAs.

Increased levels of circulating fibroblast growth factor 21 in children with Kawasaki disease.

The purpose of this study was to examine the serum levels of fibroblast growth factor 21 (FGF21) in children with acute Kawasaki disease (KD) and to investigate its relationship with coronary artery lesions (CALs). Blood samples from 58 children with KD before intravenous immunoglobulin treatment and from 28 healthy children as control group were collected. Serum FGF21 levels in all participants were measured using enzyme-linked immunosorbent assay, and clinical parameters were tested in all KD patients. Serum FGF21 levels were significantly increased in acute KD patients as compared to the control group. Serum levels of FGF21 were substantially higher in the group of KD patients with CALs (KD-CALs) than in KD patients without CALs (KD-NCALs). Positive relationships between serum levels of FGF21 and percentage of leukomonocytes (L %), C-reactive protein, activated partial thromboplastin time and D-dimer were observed in KD patients. Furthermore, serum FGF21 levels were negatively correlated with red blood cell counts, hemoglobin (Hb), percentage of neutrophils (N %) and albumin. Serum level of FGF21 is associated with inflammation and coagulation. The paradoxical increase in serum FGF21 in acute KD patients may indicate a protective compensatory response.