Treatment Of Kawasaki Disease Research Articles

The Benefits and Respective Side-Effects of PE Therapy for Intractable Kawasaki Disease.

Kawasaki disease (KD) is a vasculitis syndrome that frequently develops coronary artery lesions (CALs). In the treatment of KD, the utility of high-dose intravenous immuno-globulin (IVIG) therapy has already been clarified, and it has been established as the first-line treatment method. However, since approximately 10% of patients are refractory to this IVIG therapy and 2.6% of all patients have coronary sequelae, 500 children with KD still remain every year in Japan. In this disease, it is necessary to calm inflammation within 10 days of onset in order to suppress CALs caused by a large amount of persistent inflammatory cytokines. Indeed, the early suppression of inflammation is an effective means of suppressing the onset of CALs. Here, we describe the pathophysiology of Kawasaki disease and plasma exchange (PE), which is a therapeutic method that can calm the hyper-cytokine state of this disease. The treatment result of PE for IVIG-refractory Kawasaki disease is outstanding, and an extremely large effect can be expected if it can be started before the appearance of CALs. It seems that it should always be considered as one of the powerful additional treatments in the future.

Altered Monocyte Subsets in Kawasaki Disease Revealed by Single-cellRNA-Sequencing.

BackgroundKawasaki disease (KD) is characterized by a disorder of immune response, and its etiology remains unknown. Monocyte is an important member of the body’s innate immune system; however its role in KD is still elusive due to its ambiguous heterogeneity and complex functions. We aim to comprehensively delineate monocyte heterogeneity in healthy and KD infants and to reveal the underlying mechanism for KD.MethodsPeripheral monocytes were enriched from peripheral blood samples of two healthy infants and two KD infants. scRNA-seq was performed to acquire the transcriptomic atlas of monocytes. Bio-information analysis was utilized to identify monocyte subsets and explore their functions and differentiation states. SELL+CD14+CD16- monocytes were validated using flow cytometry.ResultsThree monocyte subsets were identified in healthy infants, including CD14+CD16- monocytes, CD14+CD16+ monocytes, and CD14LowCD16+ monocytes. Cell trajectory analysis revealed that the three monocyte subsets represent a linear differentiation, and possess different biological functions. Furthermore, SELL+CD14+CD16- monocytes, which were poorly differentiated and relating to neutrophil activation, were found to be expanded in KD.ConclusionOur findings provide a valuable resource for deciphering the monocyte heterogeneity in healthy infants and uncover the altered monocyte subsets in KD patients, suggesting potential biomarkers for KD diagnosis and treatment.

Higher efficacy of infliximab than immunoglobulin on Kawasaki disease, a meta-analysis

This meta-analysis evaluated the efficacy and safety of infliximab as initial therapy for patients with Kawasaki disease (KD) and intravenous immunoglobulin (IVIG) resistant KD. Studies of infliximab in KD, published between January 2004 and December 2019, were curated from PubMed, MEDLINE, and Cochrane Library. Data were analyzed using STATA Version 12.0. Of the 8 studies considered, 4 evaluated the effect of infliximab combined with IVIG as primary therapy in KD, and the remaining investigated the effect of infliximab in IVIG resistant patients. Infliximab was more effective than the control group, with the total summary odds ratio (OR) of 0.34 (95% confidence interval (CI): 0.19–0.62). The treatment resistance of the infliximab group was lower than the IVIG group (0.36 [95% CI: 0.14–0.92]) when infliximab was combined with IVIG as the initial treatment. However, infliximab treatment for IVIG resistant KD was more effective than the IVIG group (0.28 [95% CI: 0.12–0.66]). There was no significant increase in the incidence of coronary artery lesions. The total summary OR for the incidence of coronary artery lesions and infliximab treatment was 0.88 (95% CI: 0.48–1.62). There was no statistically significant difference in adverse events (AEs) when compared between the groups (0.71 [95% CI: 0.44–1.16]). Infliximab combined with IVIG reduced treatment resistance in KD patients vs. conventional IVIG therapy. Infliximab improved clinical course in IVIG resistant KD patients. Infliximab treatment did not reduce the incidence of coronary artery lesions and did not show any significant increase in the incidence of AEs. Prospero registration numberCRD42020218554.

A novel score system of blood tests for differentiating Kawasaki disease from febrile children.

Kawasaki disease is the most common cause of acquired heart disease among febrile children under the age of 5 years old. It is also a clinically diagnosed disease. In this study, we developed and assessed a novel score system using objective parameters to differentiate Kawasaki disease from febrile children. We analyzed 6,310 febrile children and 485 Kawasaki disease subjects in this study. We collected biological parameters of a routine blood test, including complete blood count with differential, C-reactive protein, aspartate aminotransferase, and alanine aminotransferase. Receiver operating characteristic curve, logistic regression, and Youden's index were all used to develop the prediction model. Two other independent cohorts from different hospitals were used for verification. We obtained eight independent predictors (platelets, eosinophil, alanine aminotransferase, C-reactive protein, hemoglobin, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, and monocyte) and found the top three scores to be eosinophil >1.5% (score: 7), alanine aminotransferase >30 U/L (score: 6), and C-reactive protein>25 mg/L (score: 6). A score of 14 represents the best sensitivity value plus specificity prediction rate for Kawasaki disease. The sensitivity, specificity, and accuracy for our cohort were 0.824, 0.839, and 0.838, respectively. The verification test of two independent cohorts of Kawasaki disease patients (N = 103 and 170) from two different institutes had a sensitivity of 0.780 (213/273). Our findings demonstrate a novel score system with good discriminatory ability for differentiating between children with Kawasaki disease and other febrile children, as well as highlight the importance of eosinophil in Kawasaki disease. Using this novel score system can help first-line physicians diagnose and then treat Kawasaki disease early.

Doença de Kawasaki com acometimento hepático: relato de caso de um paciente com síndrome colestática

Kawasaki disease (KD) is characterized by vasculitis in medium-caliber arteries, mainly in children under 5-years-old. The diagnosis should be made by clinical criteria, since there is no specific laboratory test. However, some laboratory and histopathological findings may help to corroborate the diagnosis, especially in inconclusive cases. The objective of this study is to report a case of a patient with a classic DK, who developed cholestatic syndrome and lymphadenopathy, requiring laboratory and pathological investigations (lymph node and hepatic biopsies) to rule out other etiologies. The clinical case described in this study exemplifies how complementary investigation can be used to rule out other etiologies and contribute to the early diagnosis and treatment of KD, which may prevent the disease from developing with complications and severe sequelae, such as coronary aneurysms.

CLINICAL-EPIDEMIOLOGICAL RELATION BETWEEN SARS-COV-2 AND KAWASAKI DISEASE: AN INTEGRATIVE LITERATURE.

ABSTRACTObjective: To analyze the current scientific literature to document, in an integrative review, the main findings that correlate Kawasaki disease (KD) to COVID-19.Data sources: The search was carried out in June 2020 in the following databases: Biblioteca Virtual em Saúde (BVS), periódico da CAPES and U.S National Library of Medicine (PubMed). The combination of descriptors used was [(COVID-19 OR SARS-CoV-2) AND (Kawasaki disease)], and the inclusion criteria stipulated were studies published from January 2019 to June 2020, without restriction of language or location, and available online in full. News, editorials, comments, and letters, as well as duplicates and articles that did not answer the guiding question were excluded.Data synthesis: A total of 97 articles were identified, of which seven comprised this review. The association of KD to the new coronavirus appears to trigger a severe clinical condition of vasculitis. Different from the usual, in this inflammatory syndrome, patients are older, and prevalence is higher in children from African or Caribbean ancestry; clinical and laboratory manifestations are also atypical, with a predominance of abdominal complaints and exaggerated elevation of inflammatory markers. In addition, there was a greater report of rare complications and greater resistance to the recommended treatment for KD.Conclusions: Pediatric COVID-19 and its potential association to severe KD, still unfamiliar to health professionals, reinforces the importance of testing patients with vasculitis for the new coronavirus and the need to wage high surveillance and preparation of the health system during the current pandemic.

Pharmacologic Interventions for Kawasaki Disease in Children: A Network Meta-Analysis of 56 Randomized Controlled Trials

Background: Although the current consensus recommends a standard treatment of high-dose intravenous immunoglobulin with high-dose aspirin to manage Kawasaki disease (KD), the use of different adjunctive therapies remains controversial. The aim of current network meta-analysis (NMA) was to compare the efficacy and tolerability of different existing interventions for the initial stage and the refractory stage of KD. Methods: The current NMA of randomized controlled trials (RCTs) was conducted under the frequentist model. Findings: Total fifty-six RCTs with 6,486 participants were included. The NMA demonstrated that the medium intravenous immunoglobulin (IVIG) + aspirin + infliximab [mean difference=−1.76 days (95% confidence intervals (95%CIs): −3.65 to 0.13 days) compared to high IVIG + aspirin] had the shortest fever duration; likewise, the medium IVIG + aspirin + infliximab [odds ratio (OR)=0.50, 95%CIs: 0.18 to 1.37 compared to high IVIG + aspirin] had the least CAL incidence in the initial-stage KD. The high IVIG + pulse steroid therapy (OR=0.04, 95%CIs: 0.00 to 0.43 compared to the high IVIG only) had the best fever subsided rate; likewise, the high IVIG + ciclosporin [OR=0.05 (95%CIs: 0.00 to 1.21) compared to the high IVIG only] had the least CAL incidence in the refractory-stage KD. Interpretation: The current NMA demonstrates that the addition of infliximab plus current standard therapy might be the best treatment for acute KD. Conversely, ciclosporin plus IVIG serves as the best choice for lower the CAL incidence in refractory KD. Further controlled trials are warranted to confirm these findings. Funding Statement: The authors of this work did not receive any grant supports. Brendon Stubbs is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR). Brendon Stubbs is part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust. Brendon Stubbs is also supported by the Maudsley Charity, King’s College London and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. Declaration of Interests: The authors report no financial interests or potential conflicts of interest.

Variation in the management of Kawasaki disease in Australia and New Zealand: A survey of paediatricians.

This study aimed to describe the current management practices for Kawasaki disease (KD) in Australia and New Zealand. We performed a secondary analysis on the Australian and New Zealand responses to a large international survey of clinicians' perspectives on KD diagnosis and management. There was general consensus among Australian and New Zealand clinicians regarding the indications for intravenous immunoglobulin and aspirin in the management of acute KD. There was less consensus on the dose of these agents, the definition and management of treatment-resistant KD and the approach to long-term thromboprophylaxis. Most clinicians use intravenous immunoglobulin for primary treatment of KD. There is variation regarding other aspects of KD diagnosis and important management issues. Future studies should confirm whether this reported variation occurs in real-world practice and assess potential impacts on patient outcome.

Prediction for Intravenous Immunoglobulin Resistance Combining Genetic Risk Loci Identified From Next Generation Sequencing and Laboratory Data in Kawasaki Disease.

Background: Kawasaki disease (KD) is the most common cause of acquired heart disease. A proportion of patients were resistant to intravenous immunoglobulin (IVIG), the primary treatment of KD, and the mechanism of IVIG resistance remains unclear. The accuracy of current models predictive of IVIG resistance is insufficient and doesn't meet the clinical expectations.Objectives: To develop a scoring model predicting IVIG resistance of patients with KD.Methods: We recruited 330 KD patients (50 IVIG non-responders, 280 IVIG responders) and 105 healthy children to explore the susceptibility loci of IVIG resistance in Kawasaki disease. A next generation sequencing technology that focused on 4 immune-related pathways and 472 single nucleotide polymorphisms (SNPs) was performed. An R package SNPassoc was used to identify the risk loci, and student's t-test was used to identify risk factors associated with IVIG resistance. A random forest-based scoring model of IVIG resistance was built based on the identified specific SNP loci with the laboratory data.Results: A total of 544 significant risk loci were found associated with IVIG resistance, including 27 previous published SNPs. Laboratory test variables, including erythrocyte sedimentation rate (ESR), platelet (PLT), and C reactive protein, were found significantly different between IVIG responders and non-responders. A scoring model was built using the top 9 SNPs and clinical features achieving an area under the ROC curve of 0.974.Conclusions: It is the first study that focused on immune system in KD using high-throughput sequencing technology. Our findings provided a prediction of the IVIG resistance by integrating the genotype and clinical variables. It also suggested a new perspective on the pathogenesis of IVIG resistance.

Multicenter retrospective study about the epidemiological, clinical and therapeutic aspects of Kawasaki disease in children from Panama

Kawasaki disease (KD) is the leading cause of pediatric acquired heart disease in many countries, however, there are few published studies from Latin America (LA). To describe the epidemiology, clinical aspects, and treatment of KD in children from Panama as part of the REKAMLATINA-2 in LA. Retrospective descriptive review of hospitalized patients diagnosed with KD, attended at three main pediatric hospitals of Panama from January-1-2009 to December-31-2013. 111 patients were analyzed, 61(54.9 %) were male. All children were hospitalized, and had a mean length of hospitalization of 5.8 (4-7) days. Median age at admission was 28.9 (12-38) months. Prior to KD final diagnosis, 63.9% patients received antibiotics for other presumed diagnoses. 105 (94.6%) patients received IGIV, 10 (9.5%) were resistant. On initial echocardiogram, 11.7% of cardiovascular complications were reported, of which coronary artery lesions (CALs) were detected in 3 (2.9 %) patients. The data suggest that KD in Panama has an incidence of about 2.05 x 100,000 in children under 15 years of age, and with a frequency 2.6 times higher in children under 3 years. A high rate of antibiotic misuse on outpatient prior to diagnostic confirmation was observed, suggesting KD unawareness and late recognition in Panamá.

Abstract 12698: Sodium-containing versus Sodium-trace Preparations of Ivig for Children With Kawasaki Disease in Acute Phase

Objectives: Kawasaki disease (KD) is an acute systemic vasculitis that most commonly causes acquired cardiac disease in children in developed countries. The most highly recommended treatment for KD is 2 g/kg intravenous immunoglobulin (IVIG). Hyponatremia in patients with KD in the acute phase is known to be associated with IVIG resistance and coronary artery abnormalities (CAA). There are two types of IVIG, sodium-containing (high Na) and sodium-trace (low Na) preparations. However, few studies have compared the effects of these two preparations for superiority. The purpose of this study was to compare outcomes between high and low Na IVIG preparations in KD children using a national inpatient database in Japan. Methods: We used the Diagnostic Procedure Combination database to identify KD patients treated with IVIG between 2010 and 2017. We identified those receiving high and low Na preparations of IVIG as an initial treatment. Outcomes included proportion of CAA, IVIG resistance, adverse effects, length of stay, and medical cost. Propensity score-matched analyses were conducted to compare the outcomes between the two groups. Instrumental variable analyses were performed to confirm the results. Results: We identified 47,292 patients with KD and created 23646 propensity score-matched pairs between the high and low Na IVIG groups. There were significant differences in proportions of CAA (2.5% vs. 2.9%; p=0.016) and IVIG resistance (23.8% vs. 24.9%; p=0.006) between the two groups. However, there were no significant differences in length of stay or medical cost. The instrumental variable analyses confirmed that high Na IVIG was significantly associated with lower proportion of CAA compared with low Na IVIG (odds ratio, 1.69; p<0.001). Conclusions: The present study suggests that high Na IVIG is potentially effective for reducing the proportion of CAA in KD patients. Prospective studies are warranted to confirm the effectiveness observed in this study.

Crucial transcripts predict response to initial immunoglobulin treatment in acute Kawasaki disease

Although intravenous immunoglobulin (IVIG) can effectively treat Kawasaki disease (KD), 10–20% of KD patients show no beneficial clinical response. Developing reliable criteria to discriminate non-responders is important for early planning of appropriate regimens. To predict the non-responders before IVIG treatment, gene expression dataset of 110 responders and 61 non-responders was obtained from Gene Expression Omnibus. After weighted gene co-expression network analysis, we found that modules positively correlated with the non-responders were mainly associated with myeloid cell activation. Transcripts up-regulated in the non-responders, IL1R2, GK, HK3, C5orf32, CXCL16, NAMPT and EMILIN2, were proven to play key roles via interaction with other transcripts in co-expression network. The crucial transcripts may affect the clinical response to IVIG treatment in acute KD. And these transcripts may serve as biomarkers and therapeutic targets for precise diagnosis and treatment of the non-responders.

The Impact of Moderate-Dose Acetylsalicylic Acid in the Reduction of Inflammatory Cytokine and Prevention of Complication in Acute Phase of Kawasaki Disease: The Benefit of Moderate-Dose Acetylsalicylic Acid.

Background: Acetylsalicylic acid (ASA) is part of the recommended treatment of Kawasaki disease (KD). Controversies remain regarding the optimal dose of ASA. We aimed to evaluate the impact of different doses of ASA on inflammation control while minimizing adverse effects in the acute phase treatment of KD. Methods: The enrolled 323 patients with KD were divided into three groups according to ASA dose: moderate-dose (30–50 mg/kg/day), high-dose (80–100 mg/kg/day), and non-ASA. Results: High-dose ASA group showed a significantly shorter duration of fever from the start of treatment to remission than other groups. Baseline level and delta score of interleukin (IL)-1, IL-6, IL-10, tumor necrosis factor-α, and transforming growth factor β were not statistically different among the groups. The number of patients who received additional treatments in the non-ASA group was more than other groups. Coronary artery dilatation was not significantly different among the groups. One patient with high-dose ASA was diagnosed with Reye syndrome. Conclusion: Different doses of ASA did not show any differences in changes of inflammatory bio-makers and cytokines. However, high-dose ASA showed occurrence of Reye syndrome, and non-ASA showed intravenous immunoglobulin refractoriness. We suggest that moderate-dose ASA may be beneficial for the treatment of patients in the acute phase of KD.

KAWASAKI DISEASE: A CASE REPORT

Kawasaki disease (KD) is a systemic vasculitis mostly affecting medium-sized arteries. Main symptoms include fever, conjunctivitis, skin and mucous membrane affection, and cervical lymphadenopahty. KD begins with acute-onset high fever, reduced general condition and frequently reduced cooperativity of children which can complicate physical examination. Further symptoms include generalized polymorphic exanthema (>90%), palmoplantar erythema (80%), symmetric non purulent conjunctivitis (80–90%), usually unilateral cervical lymphadenopathy (>1.5 cm; 50%), and mucosal enanthema with red and/or chapped lips (80–90%). A female patient of 8 months and weight 10.2kg was bought to the hospital on 17/1/2020 with the complaints of prolonged high grade fever since last 10 days, previously the baby was treated with antibiotics but the fever was not subsided. On further evaluation the child was diagnosed with KD and symptomatic treatment given along with standard immunoglobulin and aspirin. Patient was treated well and discharged. Keywords: Kawasaki ,medium sized articles, chapped lips, fever

Grisel\u2019s syndrome in Kawasaki disease

BackgroundApproximately 50–70% of patients with Kawasaki disease (KD) could present with cervical lymphadenopathy associated with deep neck inflammation, which may result in Grisel’s syndrome (GS). Given the possibility of neurological impairment owing to GS, it is important to understand the disease profile in KD. Therefore, we carried out this study to investigate this possible complication of KD, with the aim of improving pediatricians’ recognition and awareness.MethodsPatients with KD complicated by GS in our hospital were retrospectively recruited for our study. The profiles of patients with GS (n = 10) were compared to those patients without GS (n = 1254). All the available literature describing these complications of KD was reviewed.ResultsThe incidence of GS in KD was 0.6% in our population. Compared to patients without GS, KD patients with GS were older, presented with a significantly lower male:female ratio, and a higher incidence of cervical lymphadenopathy, a higher level of neutrophil count, and erythrocyte sedimentation rate. Ten articles reporting 14 KD patients with GS were reviewed. Of the total 24 patients, GS affected 7 males and 17 females, aged from 3.5 to 9 years old. Encouragingly, no delayed diagnosis and treatment of KD was found, and all patients received conservative therapy for GS, without intravenous immunoglobulin resistance, coronary artery lesions, and neurological impairment.ConclusionsGS is a rare complication of KD with an incidence of 0.6%, predominantly affecting older, female children. The overall outcome of this disorder in KD was satisfactory with conservative therapy. Pediatricians, especially pediatric surgeons, should recognize and be aware of this possible complication of KD to avoid misdiagnosis and overtreatment.

Anakinra for Treatment-Resistant Kawasaki Disease: Evidence from a Literature Review.

Kawasaki disease (KD) is one of the most common vasculitides of childhood and the main cause of acquired heart disease in developed countries. Intravenous immunoglobulin (IVIG) in association with aspirin represents the main treatment for KD. However, 10–20% of patients fail to respond to standard treatment and have an increased risk of cardiac complications. There is currently no accepted protocol for treatment of resistant cases. Several authors highlighted the role of interleukin-1 (IL-1) as a mediator of inflammation in KD and suggested the possibility of using IL-1 or its receptor as a target of therapy. The use of IL-1 inhibitors in patients with KD has been reported in the scientific literature, but data are largely limited to individual case reports and small case series. We summarized the scientific literature related to the use of anakinra, analyzing preclinical and clinical data. Thirty-eight patients have been described so far, most of them with KD-related complications. Twenty-two were described in case reports and case series, while 16 were patients from the completed KAWAKINRA phase IIa study. Almost all patients received clinical benefit, and no relevant side effects were noted. Based on this evidence, in our opinion, anakinra may be considered as an option after the failure of the first IVIG infusion, especially in patients with coronary involvement.

COVID-19 and Hyperinflammatory Syndrome in Children: Kawasaki Disease with Macrophage Activation Syndrome in Disguise?

A hyperinflammatory syndrome has been described in times of COVID-19 in children. In the setting of uncertainty due to a new virus, the so-called hyperinflammatory syndrome has been coined as a novel entity by some and is being referred to as pediatric inflammatory multisystem syndrome (PIMS). However, the characteristics of the syndrome resemble those of Kawasaki disease (KD), an inflammatory syndrome in children that can lead to coronary artery abnormalities due to a subsequent vasculitis. Furthermore, Kawasaki disease may occasionally trigger macrophage activation syndrome (MAS), a condition in which there is uncontrolled activation and proliferation of macrophages and other cell types, and could lead to multiorgan system dysfunction. This study provides a review of the data regarding COVID-19, Kawasaki disease, and macrophage activation syndrome to demonstrate the similarities and differences between the inflammatory syndrome seen with COVID-19 and KD. In addition, a framework for diagnosis and evaluation is provided that focuses on the pathway previously established for KD and MAS. The authors believe that based on current knowledge, KD treatment delays may carry deleterious effects in the near future for children with COVID-19-related Kawasaki disease.

Treatment-associated hemolysis in Kawasaki disease: association with blood-group antibody titers in IVIG products

AbstractHemolytic anemia resulting from IV Immunoglobulin (IVIG) treatment can be a serious complication, especially for those with underlying conditions with a high level of inflammation and after administration of high IVIG dosages, such as Kawasaki disease (KD), a multisystem vasculitis affecting young children. This hemolysis is caused by antibodies against blood groups A and B, but the precise mechanism for hemolysis is not known. We performed a single center, partly retrospective, partly prospective study of a cohort of 581 patients who received IVIG for treatment of KD from 2006 to 2013. Factors associated with hemolysis were identified through univariable and multivariable logistic regression. Six IVIG preparations were assayed for their hemolytic effect with serological and cellular assays to clarify the mechanism of red cell destruction. During the study period, a sudden increase in the incidence of hemolysis was observed, which coincided with the introduction of new IVIG preparations in North America that contained relatively high titers of anti-A and anti-B. These blood-group–specific antibodies were of the immunoglobulin G2 (IgG2) subclass and resulted in phagocytosis by monocyte-derived macrophages in an FcγRIIa-dependent manner. Phagocytosis was increased in the presence of proinflammatory mediators that mimicked the inflammatory state of KD. An increased frequency of severe hemolysis following IVIG administration was caused by ABO blood-group–specific IgG2 antibodies leading to FcγRIIa-dependent clearance of erythrocytes. This increase in adverse events necessitates a reconsideration of the criteria for maximum titer (1:64) of anti-A and anti-B in IVIG preparations.

Kawasaki disease: SOCS2-AS1/miR-324-5p/CUEDC2 axis regulates the progression of human umbilical vein endothelial cells

Kawasaki disease (KD) is the most prevailing cause of acquired heart disease in children, due to permanent coronary artery damage. Recently, the role of long noncoding RNAs (lncRNAs) in human diseases has been highlighted. However, the role of lncRNA SOCS2 antisense RNA 1 (SOCS2-AS1) on the function of human umbilical vein endothelial cells (HUVECs) in KD remains elusive. SOCS2-AS1 expression was examined via RT-qPCR. CCK-8, EdU, caspase-3 activity, flow cytometry and TUNEL assays were conducted for exploring the function of SOCS2-AS1 in HUVECs of KD. The interaction among RNAs (SOCS2-AS1, miR-324-5p and CUEDC2) was validated via luciferase reporter, RIP and RNA pull-down assays. SOCS2-AS1 was highly expressed in serum and tissues of KD patients. SOCS2-AS1 depletion repressed the proliferation of HUVECs, whereas it facilitated apoptosis. Further, SOCS2-AS1 could bind with miR-324-5p and negatively regulated miR-324-5p expression in HUVECs. Besides, CUE domain containing 2 (CUEDC2) was the downstream target of miR-324-5p, and SOCS2-AS1 could release CUEDC2 expression via sponging miR-324-5p in HUVECs. Furthermore, downregulating miR-324-5p or upregulating CUEDC2 could rescue the progression of HUVECs restrained by SOCS2-AS1 knockdown. SOCS2-AS1 upregulates CUEDC2 via inhibiting miR-324-5p to promote the progression of HUVECs in KD, providing new insights for KD treatment. SOCS2-AS1 is highly expressed in the serum of KD patients. SOCS2-AS1 contributes to cell proliferation in HUVECs of KD through elevating CUEDC2 expression by sequestering miR-324-5p. SOCS2-AS1/miR-324-5p/CUEDC2 axis exerts a progression-facilitating function in KD. These findings suggest SOCS2-AS1 as a novel potential target for KD treatment.

The Blood Gene Expression Signature for Kawasaki Disease in Children Identified with Advanced Feature Selection Methods.

Kawasaki disease (KD) is an acute vasculitis, accompanied by coronary artery aneurysm, coronary artery dilatation, arrhythmia, and other serious cardiovascular diseases. So far, the etiology of KD is unclear; it is necessary to study the molecular mechanism and related factors of KD. In this study, we analyzed the expression profiles of 75 DB (identifying bacteria), 122 DV (identifying virus), 71 HC (healthy control), and 311 KD (Kawasaki disease) samples. 332 key genes related to KD and pathogen infections were identified using a combination of advanced feature selection methods: (1) Boruta, (2) Monte-Carlo Feature Selection (MCFS), and (3) Incremental Feature Selection (IFS). The number of signature genes was narrowed down step by step. Subsequently, their functions were revealed by KEGG and GO enrichment analyses. Our results provided clues of potential molecular mechanisms of KD and were helpful for KD detection and treatment.