scholarly journals Association Between Serum miR-221-3p and Intravenous Immunoglobulin Resistance in Children With Kawasaki Disease

Author(s):  
Fengchuan Jing ◽  
Haobo Weng ◽  
Jing Zhang ◽  
Qiongfei Pei ◽  
Ruixi Liu ◽  
...  

Abstract ObjectivesIntravenous 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.Methods55 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). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to detect the levels of miR-221-3p.ResultsCompared 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 (ROC) curve showed that miR-221-3p had a better value for diagnosis IVIG resistance in children with KD than Kobayashi Score and the combination of both with the AUC of 0.811 (95% CI, 0.672-0.951), 0.793 (95% CI, 0.618-0.968) and 0.797 (95% CI, 0.619-0.974), respectively.ConclusionsmiR-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 of IVIG resistance in children with KD.

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yaheng Lu ◽  
Tingting Chen ◽  
Yizhou Wen ◽  
Feifei Si ◽  
Xindan Wu ◽  
...  

Abstract Background Repeated intravenous immunoglobulin (IVIG) resistance prediction is one of the pivotal topics in Kawasaki disease (KD). Those non-responders of repeated IVIG treatment might be improved by an early-intensified therapy to reduce coronary artery lesion and medical costs. This study investigated predictors of resistance to repeated IVIG treatment in KD. Methods A total of 94 children with IVIG-resistant KD treated at our hospital between January 2016 and August 2020 were retrospectively analyzed. According to the therapeutic effect of a second dose IVIG treatment, the children were divided into repeated IVIG-responsive group and repeated IVIG-resistant group, and the clinical and laboratory data were compared. Predictors of repeated IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis. Results The Pre-IVIG laboratory data showed the percentage of neutrophils (N%) and levels of serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP) were significantly higher in repeated IVIG-resistant group compared with repeated IVIG-responsive group, while levels of serum sodium and albumin (ALB) were significantly lower (P < 0.05). The post-IVIG laboratory values of N% and C-reactive protein (CRP) were significantly higher in the repeated IVIG-resistant group compared with repeated IVIG-responsive group, while hemoglobin and ALB were lower (P < 0.05). Pre-IVIG PCT and post-IVIG CRP exhibited AUC of 0.751 and 0.778 respectively in predicting repeated IVIG resistance in KD. Pre-IVIG PCT > 1.81ng/ml (OR 4.1, 95 % CI 1.4 ~ 12.0, P < 0.05) and post-IVIG CRP > 45 mg/L (OR 4.6, 95 % CI 1.3 ~ 16.2, P < 0.05) were independent predictors of repeated IVIG resistance in KD. Conclusions Our study illustrates the serum PCT level before initial IVIG treatment and CRP after initial IVIG could be used to predict repeated IVIG resistance in KD.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
Y Huang

Abstract Kawasaki disease (KD) is the most common acute coronary vasculitis disease occurring in children. Its occurrence has been attributed to the combined effects of infection, genetics, and immunity. While the etiopathogenesis of KD remains unknown, we have performed a survey of global genetic DNA methylation status and transcripts expression in KD patients to address how they contribute to the pathogenesis of KD. Methods We recruited 148 participants for this study. The chip studies consisted of 18 KD patients that were analyzed prior to administering intravenous immunoglobulin (IVIG) treatment and at least 3 weeks afterward, as well as 36 non-KD control subjects. We performed a separate cohort of 94 subjects to validate real-time quantitative PCR. Results According to the microarray study, CD177, a neutrophil surface molecule, appeared to be most significantly upregulated in KD patients compared to controls with epigenetic hypomethylation. After patients received IVIG treatment, CD177 mRNA levels decreased significantly. PCR validation indicated that the expression of CD177 is consistent with the Transcriptome Array 2.0 results. Furthermore, the area under the curve values of CD177 between KD patients and controls is 0.937. We also observed significantly higher CD177 levels in typical KD than incomplete presentation, which was associated with IVIG resistance in KD patients. Conclusion The present study is the first to highlight the epigenetic hypomethylation of an increased CD177 transcript during the acute stage of KD. Furthermore, the higher expression of CD177 in a typical presentation of KD patients and was related to IVIG resistance.


2015 ◽  
Vol 100 (4) ◽  
pp. 366-368 ◽  
Author(s):  
Sarah Davies ◽  
Natalina Sutton ◽  
Sarah Blackstock ◽  
Stuart Gormley ◽  
Clive J Hoggart ◽  
...  

The Kobayashi score (KS) predicts intravenous immunoglobulin (IVIG) resistance in Japanese children with Kawasaki disease (KD) and has been used to select patients for early corticosteroid treatment. We tested the ability of the KS to predict IVIG resistance and coronary artery abnormalities (CAA) in 78 children treated for KD in our UK centre. 19/59 children were IVIG non-responsive. This was not predicted by a high KS (11/19 IVIG non-responders, compared with 26/40 responders, had a score ≥4; p=0.77). CAA were not predicted by KS (12/20 children with CAA vs 25/39 with normal echo had a score ≥4; p=0.78). Low albumin and haemoglobin, and high C-reactive protein were significantly associated with CAA. The KS does not predict IVIG resistance or CAA in our population. This highlights the need for biomarkers to identify children at increased risk of CAA, and to select patients for anti-inflammatory treatment in addition to IVIG.


Author(s):  
Sumantra Raut ◽  
Satyabrata Roychowdhoury ◽  
Subhajit Bhakta ◽  
Mihir Sarkar ◽  
Mousumi Nandi

ABSTRACT Background Recently a severe form of COVID-19 infection has been described in a cluster of children presenting as multisystem inflammatory condition. One of the important spectrum of this condition is incomplete Kawasaki disease (KD). Case report A 5-month-old male child presented with high-spiking fever for 5 days with skin rash, bilateral non-purulent conjunctivitis and irritability. His C-reactive protein was markedly elevated (215.4 mg/l). Echocardiography revealed dilated left main coronary artery (3.0 mm, Z score +4.30) and left anterior descending artery (2.37 mm, Z score +3.76). Concomitantly Reverse Transcription- Polymerase Chain Reaction for COVID-19 was positive on fifth day sample. He was diagnosed as incomplete KD with COVID-19 infection and treated with intravenous immunoglobulin (IVIG) (2 g/kg), oral aspirin and azithromycin. Patient improved after 48 h and was discharged on oral aspirin. Conclusion Incomplete KD may co-exist with COVID-19 infection in infant. Early institution of IVIG may lead to better outcome.


2021 ◽  
Author(s):  
Yaheng Lu ◽  
Tingting Chen ◽  
Yizhou Wen ◽  
Feifei Si ◽  
Xindan Wu ◽  
...  

Abstract Background: Repeated intravenous immunoglobulin (IVIG) resistance prediction is one of the pivotal topics in Kawasaki disease (KD). Those non-responders of repeated IVIG treatment might be improved by an early-intensified therapy to reduce coronary artery lesion and medical costs. This study investigated predictors of resistance to repeated IVIG treatment in KD.Methods: A total of 94 children with IVIG-resistant KD treated at our hospital between January 2016 and August 2020 were retrospectively analyzed. According to the therapeutic effect of a second dose IVIG treatment, the children were divided into repeated IVIG-responsive group and repeated IVIG-resistant group, and the clinical and laboratory data were compared. Predictors of repeated IVIG resistance and the optimal cut-off value were determined by multiple logistic regression analysis and receiver operating characteristic (ROC) curve analysis.Results: The laboratory data of the percentage of neutrophils (N%) and levels of serum procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP) on admission were significantly higher in repeated IVIG-resistant group compared with repeated IVIG-responsive group, while levels of serum sodium (Na+) and albumin (ALB) were significantly lower (P<0.05). The clinic data showed no significant differences between the two groups. PCT exhibited the largest AUC (0.751) in predicting repeated IVIG resistance in KD compared with N%, Na+, ALB, and NT-proBNP. PCT>1.81ng/ml was an independent predictor of repeated IVIG resistance in KD (OR 4.161, 95% CI 1.441~12.017, P=0.008). Conclusions: Our study illustrates the serum PCT level before initial IVIG treatment could be used to predict repeated IVIG resistance in KD.


Author(s):  
Shuran Shao ◽  
Kaiyu Zhou ◽  
Xiaoliang Liu ◽  
Lei Liu ◽  
Mei Wu ◽  
...  

Abstract Context Intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs) prediction are pivotal topic of interests in Kawasaki disease (KD). However, data on the predictive value of lipid profile for both IVIG resistance and CALs are limited. Purpose To investigate the predictive validity of lipid profile for IVIG resistance and CALs in KD. Design Prospective cohort study. Setting West China Second University Hospital. Patients 363 KD patients were divided into the initial IVIG-resistant group and initial IVIG-responsive group; repeated IVIG-resistant group and repeated IVIG-responsive group; CAL+ group and CAL- group. Main Outcome Measures Validity of lipid profile in predicting IVIG resistance and CALs. Results TG was significantly higher whereas TC, HDL-C, LDL-C as well as Apo A were significantly lower in initial IVIG-resistant subjects, with cut-off values of 1.625 mmol/L, 3.255 mmol/L, 0.475 mmol/L, and 1.965 mmol/L and 0.665 g/L, yielding sensitivities of 52%, 70%, 52%, 61%, 50%, and specificities of 68%, 53%, 78%, 71%, 81%, respectively. TC, LDL-C, and Apo A levels were significantly lower in repeated IVIG-resistant subjects, with cut-off values of 3.20 mmol/L, 1.78 mmol/L, 0.605 g/L, producing sensitivities of 91%, 70%, 57% and specificities of 55%, 67%, 70%, respectively. Apo-A level was significantly lower in the CAL group, with cut-off value of 0.805g/L, yielding sensitivity of 66% and specificity of 54%. Conclusions Lipid profiles were significantly dysregulated in KD patients suffering IVIG resistance and CALs. Some of them, such as LDL-c and Apo-A, could serve as complementary laboratory markers for predicting both IVIG resistance and CALs.


2019 ◽  
Vol 57 (7) ◽  
pp. 1063-1072 ◽  
Author(s):  
Wei Zong ◽  
Wei Feng ◽  
Yun Jiang ◽  
Shaoqing Ju ◽  
Ming Cui ◽  
...  

Abstract Background Long non-coding RNAs (lncRNAs) have been reported to play a key role in gastric cancer (GC) tumorigenesis. However, the clinical application value of serum lncRNAs in GC has remained largely unknown. We investigated the role of a novel lncRNA named CTC-497E21.4 in the diagnosis and the prognosis of GC. Methods We focused on evaluation of lncRNA CTC-497E21.4 by real-time fluorescent quantitative polymerase chain reaction (RTFQ-PCR). The study involved following aspects: (1) confirmation of the higher lncRNA CTC-497E21.4 expression in different types of GC specimens than corresponding controls; (2) evaluation of monitoring tumor dynamics by the serum lncRNA CTC-497E21.4 assay; (3) evaluation of the prognostic value of lncRNA CTC-497E21.4 assay in GC. Results (1) The method of RTFQ-PCR detection of lncRNA CTC-497E21.4 was evaluated to have high sensitivity and specificity. (2) The expression levels of lncRNA CTC-497E21.4 were higher in GC patients compared with corresponding controls (p<0.001), and the combination of serum lncRNA CTC-497E21.4, CEA and CA19-9 could improve diagnostic sensitivity (96.36%). (3) The serum lncRNA CTC-497E21.4 expression levels were lower in postoperative samples than preoperative samples (p=0.0021) and survival curves downloaded from TCGA showed high lncRNA CTC-497E21.4 levels were associated with poor OS of GC (p=0.0351). Conclusions lncRNA CTC-497E21.4 may be a potential biomarker for the diagnosis and the prognosis of GC.


2021 ◽  
Vol 7 (3) ◽  
pp. 018-027
Author(s):  
Toshimasa Nakada

Kawasaki disease (KD) is an acute febrile systemic vasculitis that primarily affects children younger than 5 years, with coronary artery lesions (CALs) as its severe complications. Intravenous immunoglobulin (IVIG) therapy resistance has been implicated in CAL development, and its known predictors are as follows: Egami score, Kobayashi score, C-reactive protein (CRP), albumin, CRP-to-albumin ratio, and neutrophil-to-lymphocyte ratio (NLR). However, the most useful predictor for IVIG resistance in patients with KD without complications before initial acute-phase treatment remains unclear. Therefore, this study aimed to determine the most useful predictor for IVIG resistance in such patients. This retrospective study included data from 202 patients with KD who underwent acute-phase treatment from January 2009 to March 2021. Among 46 IVIG-resistant patients, 22 patients required rescue therapy (rescued patients), while the remaining 24 received no rescue therapy for resistance and had no CALs. Among the 6 indices, NLR had the highest sensitivity and specificity for the detection of all IVIG-resistant patients and rescued patients (0.724 and 0.728, respectively), and logistic regression analysis showed that the NLR was the sole independent predictor both for the IVIG-resistant patients and for the rescued patients (P < 0.001 and = 0.002, Odds ratio = 5.797 and 5.814, 95% confidence interval = 2.687–12.504 and 1.954–17.299, respectively). NLR was the useful predictor for all IVIG-resistant patients and rescued patients among those with KD without complications before initial acute-phase treatment.


Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 466
Author(s):  
Hwa Jin Cho ◽  
Woo Young Kim ◽  
Sung Man Park ◽  
Jung Hwa Lee ◽  
Hong Ju Shin ◽  
...  

Background and Objectives: Most cases of Kawasaki disease (KD) occur between the ages of 6 months and 5 years. Differences in immunological reaction and CAL (coronary artery lesion) by the age subgroups classified according to the prevalence of KD and those particularly in the earlier life of KD should be investigated. Materials and Methods: The laboratory data of 223 infantile and 681 non-infantile KD cases from 2003 to 2018 at Korea University Hospital were retrospectively analyzed. Patients with KD were divided into infants and non-infants and further subdivided into four subgroups by age. The age-adjusted Z-values were compared among the subgroups. Febrile controls were identified as patients with fever for >5 days and who showed some of the KD symptoms. Results: IVIG (intravenous immunoglobulin) resistance at the age of 6 months or less was significantly lower than that at the ages of 7–12 months and 13–60 months (respectively, p < 0.05). The significant risk factors for CAL in total KD patients were age, incomplete KD, post-IVIG fever, IVIG resistance, convalescent Z-eosinophil, and subacute platelet (p < 0.05). The significant risk factors for CAL at the age of 6 months or less were IVIG resistance, acute Z-neutrophil, subacute Z-neutrophil, subacute NLR (neutrophil to lymphocyte ratio), and subacute platelet (respectively, p < 0.05). Conclusion: Younger age and incomplete presentation in KD can be independent risk factors for CAL. The immune reactions of KD at a younger age are more tolerated compared with those at older ages during the acute phase. The immune response at the age of 6 months or less showed immune tolerance in terms of incomplete presentation and IVIG responsiveness. The risk factors such as IVIG resistance, subacute platelet, subacute NLR, and acute or subacute Z-neutrophil at the age of 6 months or less can be very useful parameters to predict CAL in young, incomplete KD.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Shuran Shao ◽  
Chunyan Luo ◽  
Kaiyu Zhou ◽  
Yimin Hua ◽  
Mei Wu ◽  
...  

Abstract Background The prediction of resistance to intravenous immunoglobulins (IVIG) is currently still one of the main research areas in Kawasaki disease (KD). Several studies have reported on the use of N-terminal pro-brain natriuretic peptide (NT-ProBNP) to this end. However, considering the age-dependency of NT-ProBNP levels, age- specific NT-ProBNP cutoff levels to predict IVIG resistance in KD might be more precise and should be evaluated. Methods A prospective cohort study with standardized data collection involving 393 KD patients aged 1 month to 125 months was conducted between June 2015 and April 2018. The demographic characteristics, clinical manifestations and laboratory data were compared between the patients responding to initial intravenous immunoglobulin (IVIG-response group) and those who did not (IVIG-resistance group). We further distinguished four subgroups according to patients’ age (< 1 year, 1–2 years, 2–6 years, > 6 years). The cutoff values of NT-ProBNP for the prediction of IVIG resistance overall and in the subgroups were obtained using receiver operating characteristic (ROC) analysis. Results In all KD patients, the level of NT-ProBNP was significantly higher in the IVIG-resistance compared to the IVIG-response group (P = 0.006). This findings was similar in the subgroups except for patients older than six years. The best cutoff values of NT-ProBNP to predict IVIG resistance were 3755 pg/ml for all KD patients, 3710 pg/ml, 2800 pg/ml, 2480 pg/ml for those aged 2–6 years, 1–2 years and < 1 year, respectively. The corresponding sensitivities were 44.0, 52.2, 50.0 and 75.0%, while the specifities were 84.1, 86.3, 77.9 and 71.8%, respectively. Conclusions NT-proBNP is a complementary laboratory marker for the prediction of IVIG resistance in KD patients, particularly for those younger than one year. Applying age-specific cutoff values is more precise than one value for all ages.


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