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Background Attention-deficit/hyperactivity disorder (ADHD) has been linked to pediatric asthma patients treated with montelukast. This study is the first to use a nationwide health insurance research database (NHIRD) to study whether asthmatic children using montelukast are at an increased risk of ADHD. Methods We used data from the Taiwan NHIRD, which is a longitudinal database of one million randomly selected subjects. The enrolled patients were followed up until 2013. Patients younger than and equal to 12 years old with new-onset asthma (ICD-9 CM code 493.X) diagnosed between 1997 and 2013 were enrolled. A multivariate Cox regression analysis was conducted to evaluate the association between montelukast treatment and the risk of ADHD (ICD-9-CM code 314.X). Results We enrolled a total of 54,487 asthmatic children younger than and equal to 12 years old who had at least one claim of inpatient admission or at least three claims of an ambulatory visit. Montelukast users and match controls were identified by matching age, gender, residence, the comorbidities including allergic rhinitis and atopic dermatitis, admission or emergency department visits due to asthma attack, and index date of starting montelukast in a 1:1 ratio, with 12,806 in the montelukast group and 12,806 in the non-montelukast group. The montelukast group had a similar risk of ADHD (n = 632, 4.94%) as the non-montelukast group (n = 610, 4.76%) [adjusted hazard ratio 1.04; 95% confidence interval, 0.93 to 1.17]. In children treated with montelukast, high cumulative days of montelukast use did not increase the risk of ADHD. Conclusion This nationwide population-based cohort study reveals that asthma children treated with montelukast were not at an increased risk of developing ADHD. Nevertheless, validation of our retrospective survey requires further prospective study.

BackgroundKawasaki disease (KD) causes coronary artery lesions (CAL) and is the leading cause of acquired heart disease in children. The aim of this study is to evaluate the risk factors and set-up a scoring system for predicting CAL of KD.MethodsWe retrospectively reviewed a total of 478 patients diagnosed with KD. We compared age, gender, laboratory data, and treatment response in two groups and developed a scoring system for predicting CAL.ResultsDuring the study period, 365 of these patients had complete medical records of coronary surveys by echocardiography. Anemia, hypoalbuminemia, C reactive protein (CRP), alanine aminotransferase, neutrophil count, and neutrophil/lymphocyte ratio (NLR) showed significant differences with CAL formation. We determined the cut-off value using a receiver-operating-characteristic (ROC) curve, and following multivariate logistic regression analysis, four independent risk factors demonstrated a significant difference with CAL formation, including CRP > 103 mg/L, NLR > 3.5, male gender, and intravenous immunoglobulin (IVIG) resistance. We established a score system based on the above evaluation, for which a ROC curve was performed, and a total score of ≥ 2 points showed a sensitivity of 60.8% and a specificity of 70.6%, with an area under the ROC curve of 0.696.ConclusionsIdentifying children at risk is important in order to prevent CAL from developing. Four independent risk factors that can predict CAL formation were CRP > 103 mg/L, NLR > 3.5, male gender, and IVIG resistance. This first report incorporated NLR into score systems to predict CAL reinforces previously well-known risk factors for the CAL formation among KD patients.

Introduction: Kawasaki disease (KD) is a form of systemic vasculitis that can lead to complications of coronary artery lesions (CAL). Diagnosis without delay and treatment with intravenous immunoglobulin (IVIG) are vital for a better prognosis. Anti-inflammatory drugs are generally used empirically in pediatric patients as off label. Corticosteroids are effective with anti-inflammatory effects applied in vasculitis.Areas covered: The timing of corticosteroid treatment in KD has been widely discussed by scholars. Some corticosteroids may still be effective which could be useful for such specific populations as high-risk patients. In this narrative review, we searched clinical studies, meta-analyzes, and systemic reviews using the PubMed database to summarize the available evidence on corticosteroid usage in KD through October 2019 and then discussed the relevant issues.Expert opinion: Today, the available evidence is more powerful to recommend corticosteroids for KD, moving from an unproven therapy to an effective adjunctive treatment. We suggest using methylprednisolone pulse therapy as an alternative rescue therapy for immunoglobulin-resistant KD, as well as identifying high-risk patients who need initial corticosteroid with IVIG treatment with an adequate route, dose, and duration. In the future, studies that evaluate the precision role of corticosteroids for individualized KD patients with CAL are warranted.

Kawasaki disease (KD) is associated with expression and methylation of Fc gamma receptor genes. We characterized immunoglobulin A (IgA), IgE, IgG, and IgM receptor expression levels in KD. Fc receptor expression levels were characterized using GeneChip Human Transcriptome Array 2.0 (HTA 2.0) with 18 KD patients, 18 non-febrile controls, and 18 febrile controls. Another 48 control individuals and 46 patients with KD were measured using pyrosequencing for the methylation levels. The mRNA expression levels of FCER1A and FCER2 were significantly lower in KD patients than in non-febrile controls and then rose following treatments with intravenous immunoglobulin (IVIG). Expression levels of FCER1G increased compared to the non-febrile subjects and then subsided after IVIG. FCER1A methylation was significantly lower among KD patients and even lower in KD patients with IVIG resistance. HTA analysis revealed higher mRNA levels of FCAR, FCGR1C, and FCGR2A in KD patients. FCMR mRNA expression levels were significantly lower in KD patients. FCMR expression levels rose after IVIG treatment. After IVIG, FCGR1A, B, and C decreased even lower than the febrile controls. This is the first study indicating that IgA, IgE, IgG, and IgM receptors are associated with KD. We highlighted potential biomarkers related to Fc receptors and their regulation.

ObjectiveKawasaki disease (KD) is an acute form of febrile vasculitis that occurs in early childhood. The multisystemic vasculitis common in patients with KD may influence blood perfusion in the brain, and thus caregivers of children with KD may feel stress with regard to caring for them. Intravenous immunoglobulin (IVIG) infusion is the standard treatment for acute KD, and the most serious complication of KD is coronary artery aneurysms (coronary artery lesion (CAL)). This study aimed to investigate the relationships between KD heterogeneity and the risk of patients’ cognitive impairment or caregivers’ parenting stress.DesignA case–control study with consecutive sampling.SettingA medical centre (Kaohsiung Chang Gung Memorial Hospital, Taiwan).ParticipantsThis study consisted of 176 patients with KD (mean age: 5.5 years, 60.8% boys) and 85 healthy children (mean age: 6.4 years, 54.1% boys).Primary and secondary outcome measuresBased on the children’s age, each patient with KD and control subject was administered an assessment using the Mullen Scales of Early Learning or the Wechsler Intelligence Scale, and parenting function of their caregivers was assessed using the Parenting Stress Index (PSI)-Short Form.ResultsWe observed no significant differences in any developmental index, cognitive function or parenting stress between patients with KD and controls. Among the children with KD, IVIG administration nor CAL was associated with children’s cognitive scores. However, the caregivers of patients who had CAL suffered from greater PSI total scores than those of patients without CAL. Furthermore, the caregivers who had education levels of a master’s degree or above showed less parenting stress than those who had an education level of college or lower.ConclusionCaregivers’ education is associated to parenting stress, and caregivers of patients with KD who developed CAL may feel stress about the unpredictable sequela caused by CAL for their children. Such caregivers may require support to fulfil their parenting roles.

The Fc gamma receptor family contains several activating receptors and the only inhibitory receptor, FcγR2B. In this study, we investigated the dynamic methylation change of FcγR2B in different stages of Kawasaki disease (KD). We enrolled a total of 116 participants, which included patients with febrile diseases as controls and KD patients. Whole blood cells of KD patients were collected prior to intravenous immunoglobulin (IVIG) treatment (KD1), three to seven days after IVIG (KD2), three weeks after IVIG treatment (KD3), six months after IVIG (KD4), and one year after IVIG treatment (KD5). In total, 76 KD patients provided samples in every stage. Leukocytes of controls were also recruited. We performed DNA extraction and pyrosequencing. FcγR2B methylation levels were higher in KD3 compared to both the controls and KD1. A significantly higher methylation of FcγR2B was found in KD5 when compared with KD1. FcγR2B methylation levels in the IVIG-resistant group were lower than those in the IVIG-responsive group at KD1-3 (p = 0.004, 0.004, 0.005 respectively). This study is the first to report the dynamic change of FcγR2B methylation and to demonstrate long-term hypermethylation one year after disease onset. Hypomethylation of FcγR2B is associated with IVIG resistance.

(1) Background: Desquamation is a common characteristic of Kawasaki disease (KD). In this study, we analyzed patients’ varying desquamation levels in their hands or feet, in correlation with clinical presentation, to assess the relationship. (2) Methods: We retrospectively reviewed children with KD. We analyzed their age, laboratory data before intravenous immunoglobulin (IVIG) treatment and coronary artery abnormalities (CAA) based on the desquamation level of their hands and feet. We classified the desquamation level from 0 to 3 and defined high-grade desquamation as grade 2 and 3. (3) Results: We enrolled a total 112 patients in the study. We found the hands’ high-grade desquamation was positively associated with age and segmented neutrophil percentage (p = 0.047 and 0.029, respectively) but negatively associated with lymphocyte and monocyte percentage (p = 0.03 and 0.006, respectively). Meanwhile, the feet’s high-grade desquamation was positively associated with total white blood cell counts (p = 0.033). Furthermore, we found that high-grade hand desquamation had less probability of CAA formation compared with that of a low grade (7.1% vs. 40.8%, p = 0.016). (4) Conclusions: This report is the first to demonstrate that the desquamation level of hands or feet in KD is associated with different coronary artery abnormalities and laboratory findings.

Background: Kawasaki disease (KD) is an inflammatory disorder with an unknown etiology. It is the leading cause of acquired heart disease, which leads to coronary vasculitis among children. Studies of frequent manifestation of allergic diseases in children with KD have been the subject of mounting clinical interest. However, evidence supporting the association between KD and allergies has yet to be systematically reviewed.Methods: In this article, we reviewed current literature regarding the association between KD and allergic diseases. References for this review were identified through searches of PubMed, Cochrane, and Embase through the end of August 2020.Results: The results of the analyses of immune repertoire, clinical, and epidemiological studies have indicated some of the characteristics of infectious disease for KD. Although some allergic disorders, such as asthma, may be exacerbated by viral infections, allergies are typically caused by an allergen that triggers an immune response, with the potential involvement of type 2 inflammation and immune disturbances leading to tissue remodeling in genetically susceptible hosts. The effect of intravenous immunoglobulin is multi-faceted and results in a decrease in activating Fc gamma receptor IIA and an increase in anti-inflammatory eosinophils. The findings from this review demonstrate that children who have suffered from KD are more likely to have allergic rhinitis than the general population and their siblings, a condition that lasts until the age of 17. When followed up as teenagers and adults, children with KD are more likely to develop urticaria.Conclusions: This review supports that allergic diseases, such as allergic rhinitis, have been demonstrated to increase following KD. Therefore, the importance of allergic diseases in patients with KD should be emphasized in long-term care. Interventions that include strategies for managing allergies in children with KD would be beneficial.

Introduction: Kawasaki disease (KD) is a childhood illness causing blood vessel inflammation. Children with KD have similar cardiopulmonary function to healthy children, but lower moderate-to-vigorous activity and exercise self-efficacy&mdash, possibly harming their cardiopulmonary function in adolescence. The purpose of this study is to investigate the cardiopulmonary function, exercise behaviors, exercise motivations, and self-efficacy of adolescents who once had KD. Methods: adolescents who once had KD and adolescents matched to the KD group in age and sex were enrolled. The cardiopulmonary exercise test was used to assess cardiopulmonary function. Weekly exercise behavior, exercise motivation, and self-efficacy were assessed with questionnaires. Results: this study recruited 50 and 30 participants, respectively, to the KD and control groups. The KD group had a lower ratio of VO2/kg at the anaerobic threshold and peak to the predicted VO2/kg at the peak (p = 0.021 and 0.043, respectively). No significant differences were found in questionnaire scores. The correlations of weekly exercise behavior scores with exercise motivation and self-efficacy scores were stronger in the KD group. Conclusions: adolescents with KD history had significantly lower aerobic metabolism capacity and peak exercise load capacity than controls. The correlations of amount of weekly exercise with exercise motivation and self-efficacy were stronger in the KD group.

Background Kawasaki disease (KD) is a form of vasculitis that primarily affects children under the age of 5 years old. Patients may be missed or diagnosis delayed when initial clinical symptoms do not fulfill the traditional criteria or a normal echocardiography was found. In this study, we aimed to analyze factors that clinicians could use to differentiate febrile children suspected of KD. Method We retrospectively enrolled in this study a total of 50 febrile children who were initially suspected of KD, but they did not meet the American Heart Association (AHA) criteria for a diagnosis. However, some of these patients were diagnosed with KD during their second visit. We analyzed patients' characteristics, clinical symptoms, and laboratory data (initial data in the first visit). Results In total, 50 patients were enrolled in the study. Of those, ten patients were diagnosed with KD on their second visit (group 1), while the other 40 patients still did not fit a KD diagnosis (group 2). A higher neutrophil-to-lymphocyte ratio (NLR, p=0.037) and higher C-reactive protein levels (CRP, p=0.02) were found in group 1 when compared to group 2. A patient with a NLR greater than 1.33 combined with a CRP more than 33 mg/L was more likely to have KD (Sensitivity 90%, specificity 69.2%, p=0.001; Odds ratio 20.25, 95% confident interval 2.3-178.25). Conclusion Among patients suspected of KD that did not initially meet the criteria, clinicians should pay special attention to elevated neutrophil-to-lymphocyte ratios and CRP levels and closely follow up such patients.

This study aimed to investigate whether children with atopic diseases exhibited different neurodevelopment function from healthy controls and whether their caregivers had differential parental stress. In total, we recruited 109 patients with atopic diseases (mean age 6.8 years, 54.1% male) and 82 healthy children (mean age 6.3 years, 54.9% male). Based on the children’s age, they underwent developmental, cognitive evaluations and attention deficit/hyperactivity disorder (ADHD) symptoms. The parenting stress of children’s caregivers was evaluated using the Chinese Health Questionnaire (CHQ-12) and Family APGAR. Of the children with atopic diseases, 87.2%, 74.3%, 29.4%, and 8.3% of them had allergic rhinitis, asthma, atopic dermatitis, and urticaria, respectively. None of these conditions were associated with children’s cognitive profiles or ADHD symptoms. However, the caregivers of patients who had asthma suffered from higher CHQ-12 scores than those of patients without asthma. Furthermore, the number of atopic diseases had a dose–response effect on caregivers’ CHQ-12 scores. In conclusion, allergic diseases did not impair the cognitive development of children. However, caregivers of patients with asthma or multiple atopic diseases may suffer a greater mental health burden with regard to caring for their children. Such caregivers may require support to effectively fulfill their parenting roles.

Among the anti-inflammatory medications used for treating asthma, corticosteroids are the most effective. The effects of orally administered corticosteroids on intraocular pressure and lens opacity have been well defined, but the influence of inhaled corticosteroids (ICS) on children has yet to be clearly explained. Therefore, we used a nationwide cohort database to investigate glaucoma in childhood asthma patients using ICS. We analyzed a dataset of 1,000,000 randomly sampled individuals from Taiwan's 2000 National Health Insurance Research Database. The study cohort included 5,380 patients who were first diagnosed with asthma (ICD9: 493.X) diagnosis when they were six years old or younger. All subjects were followed through December 2011. We applied Cox's proportional hazard model to determine whether ICS use has a correlation with glaucoma. Of the 5,380 patients enrolled in this study, we identified 1,232 patients who had used ICS and 4,148 patients who had no history of ICS administration throughout the follow-up period. The prevalence of glaucoma was significantly lower in patients using ICS, with a 0.52-fold decreased risk of developing glaucoma in comparison to the control group [adjusted hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.28∼0.96]. Among the evaluated comorbidities, cataract was positively associated with glaucoma in asthma children (adjusted HR 8.22; 95% CI = 2.59∼26.12). This study provides not only the first but also strong evidence that the glaucoma incidence in the ICS group is lower than that in the non-ICS group in children with asthma. Further consultation with an ophthalmologist regarding the high-risk group of asthma children with cataracts is necessary.

Background Immunoglobulin (Ig) M plays an important role in immune regulation. FCMR-encoded FcμR is a receptor of IgM. Previous research has suggested that IgM levels may be involved in the coronary artery lesions of Kawasaki syndrome or Kawasaki disease (KD). In this study, we aimed to explore the roles of mRNA expressions of IgM receptors, particularly FCMR, in KD patients. FCMR encodes the Fc fragment of immunoglobulin M receptor. Methods We enrolled 60 KD patients and 55 non-KD controls. Whole-blood leukocytes were isolated, and the mRNA expression for FCMR was determined. Each mRNA consisted of a sample taken before intravenous immunoglobulin (IVIG) was administered (acute, KD1) and those taken at three weeks, six months, and one year later (KD3, KD4, KD5). Paired KD subjects were analyzed from both the acute and convalescent phases (n = 28). Results After six months and one year of treatment, KD patients still apparently have lower FCMR compared with controls (P = .004). FCMR expressions were downregulated in male patients with KD prior to IVIG administration (P = .044). The FCMR of paired KD patients who received IVIG treatments after six months was significantly lower than before undergoing IVIG treatment (P = .044). Expressions in the polymorphonuclear leukocytes were similar to those in the peripheral blood mononuclear cells. Conclusion The unique data supported that FCMR is expressed by granulocytes at RNA levels in humans and demonstrated lower FCMR six months after the onset of KD. The findings remind us of the need to track the health of children with KD over the long term, even if we think patients have fully recovered.

Background Although the sternoclavicular joint (SCJ) may be involved in ankylosing spondylitis, rheumatic arthritis, and Behçet’s disease and participates in the systemic inflammatory process of arthritis, it is often neglected during routine rheumatologic clinical examinations. To the best of our knowledge, this is the first study to report etanercept treatment in juvenile idiopathic arthritis (JIA) with SCJ involvement. Case presentation In this study, we describe an unusual case of a child with juvenile idiopathic arthritis with an initial presentation of sternoclavicular mass. The patient (age, 14 years 10 months) presented with an insidious onset atraumatic swelling of the left SCJ and complained of right hip and bilateral ankle tenderness without an apparent cause. Initial ultrasonography indicated a heterogeneous mass in the left SCJ, while computed tomography identified mild swelling of the left SCJ with a thickened synovial lining, mild bone erosion, and some turbid fluid. The patient ultimately underwent left SCJ arthrotomy, during which tapping of the SCJ revealed 2 cc of yellowish fluid, inflammation and necrosis of tissues within the SCJ. A clear yellow joint fluid was aspirated, and testing revealed a negative culture result. The patient was diagnosed with JIA. The joint tenderness improved and erythrocyte sedimentation rate decreased after administering anti-tumor necrosis factor etanercept. An additional ultrasonography demonstrated that the initial imaging findings have been resolved. At the end of a 2-year follow-up period, the patient was completely symptom-free. Conclusions JIA with SCJ involvement is an uncommon presentation in adolescents. Etanercept may be a beneficial treatment for SCJ involvement in patients with JIA. The upper limbs showed no signs of limited range of motion during the follow-up period. Further studies are warranted to elucidate the efficacy of etanercept in JIA with sternoclavicular joint involvement.

Kawasaki disease (KD) is a common systemic vasculitides in children younger than 5 years of age. Activated macrophages are key drivers of vascular inflammation in KD. The aim of this study was to examine differences in M1 and M2 macrophage marker expression in patients with KD. Blood samples were obtained from 18 healthy controls and 18 patients with KD at 24 h prior and 21 days after to intravenous immunoglobulin therapy. GeneChip Human Transcriptome Array 2.0 and Illumina HumanMethylation450 BeadChip were used to examined the mRNA expression and corresponding CpG site methylation ratios of 10 M1 surface markers and 15 M2 surface markers. Of the markers examined 2 M1 markers (TLR2, IL2RA) and 8 M2 markers (ARG1, CCR2, TLR1, TLR8, TLR5, MS4A6A, CD36, and MS4A4A) showed increased mRNA expression in the acute phase of KD which decreased after IVIG therapy (P < 0.05). Corresponding CpG sites in the promoter regions these markers were hypomethylated in the acute phase of KD and significantly increased after IVIG therapy. In conclusion, both M1 and M2 markers showed increased mRNA expression in the acute phase of KD. CpG site methylation may be one of the mechanisms governing macrophage polarization in KD.

Background The etiology of Kawasaki disease (KD) is still unknown; perinatal factors may have role with few studies. This study was aim to survey the perinatal factors and clinical outcome of KD, including coronary artery lesion (CAL) formation and intravenous immunoglobulin (IVIG) treatment response. Methods We enrolled a total of 185 KD patient–caregiver dyads in this study using questionnaires. The questionnaire included two categories: children’s characteristics, which consisted of age at disease onset, gender, gestational age at delivery, birth body weight, delivery methods, and breastfeeding status, and caregivers’ characteristics, which consisted of parents or not, education levels, maternal age at giving birth, total number of offspring, and family income. We analyzed the association of these factors with CAL formation and IVIG treatment response of KD. Results KD patients with CAL formation had a higher maternal age than non-CAL patients (32.49 ± 3.42 vs. 31.01 ± 3.92 years, p = 0.016). We also found that maternal age ≥ 32 years group had a higher rate of having KD patients with CAL (39/81 vs. 24/74, odds ratio 1.935, 95% confidence interval [1.007, 3.718], p = 0.047). The maternal age ≥ 35 years group had a higher rate of having KD patients with IVIG resistance (6/31 vs. 6/116, odds ratio 4.400, 95% confidence interval [1.309, 14.786], p = 0.01). There was no significant difference in either CAL formation or IVIG resistance in KD with regard to patient’s age at disease onset, gestational age, birth body weight, delivery methods, breastfeeding, caregiver type, caregivers’ education level, total number of offspring, or family income (p > 0.05). Conclusions This study is the first to report that maternal age is significantly associated with CAL formation and IVIG resistance in KD. We hypothesize that a maternal age less than 32 years would benefit KD offspring.

// Ling-Sai Chang 1,2,3 , Mao-Hung Lo 1,3 , Sung-Chou Li 4 , Ming-Yu Yang 2,5 , Kai-Sheng Hsieh 1,3 and Ho-Chang Kuo 1,3 1 Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan 2 Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Kaohsiung, Taiwan 3 Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 4 Genomics and Proteomics Core Laboratory, Department of Medical Research, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 5 Department of Otolaryngology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan Correspondence to: Ming-Yu Yang, email: // Kai-Sheng Hsieh, email: // Ho-Chang Kuo, email: // Keywords : coronary artery lesions; FcγRIIA; FcγRIIB; intravenous immunoglobulin; Kawasaki disease; Immunology and Microbiology Section; Immune response; Immunity Received : July 15, 2016 Accepted : November 14, 2016 Published : November 21, 2016 Abstract Previous research has found patients with the FcγRIIIB NA1 variant having increased risk of intravenous immunoglobulin (IVIG) resistance in Kawasaki disease (KD). Our previous studies revealed that elevated FcγRIIA expression correlated with the susceptibility of KD patients. We conducted this research to determine whether and how Fcγ receptors affect the susceptibility, IVIG treatment response, and coronary artery lesions (CAL) of KD patients. The activating FcγRIIA and inhibitory FcγRIIB methylation levels of seven patients with KD and four control subjects were examined using HumanMethylation27 BeadChip. We enrolled a total of 44 KD patients and 10 control subjects with fevers. We performed real-time RT-PCR to determine the FcγRIIA and FcγRIIB expression levels, as well as a luciferase assay of FcγRIIA . We found a considerable increase in methylation of both FcγRIIA and FcγRIIB in KD patients undergoing IVIG treatment. Promoter methylation of FcγRIIA inhibited reporter activity in K562 cells using luciferase assay. The FcγRIIB mRNA expression levels were not found to increase susceptibility, CAL formation, or IVIG resistance. FcγRIIA mRNA expression levels were significantly higher in IVIG-resistant patients than in those that responded to IVIG during the pre-treatment period. Furthermore, the FcγRIIA/IIB mRNA expression ratio was considerably higher in KD patients with CAL than in those without CAL. FcγRIIA and FcγRIIB both demonstrated increased methylation levels in KD patients that underwent IVIG treatment. FcγRIIA expression influenced the IVIG treatment response of KD patients. The FcγRIIA/IIB mRNA expression ratio was greater in KD patients with CAL formation.

The risk of ethnic Kawasaki disease (KD) has been proposed to be associated with blood mercury levels in American children. We investigated the blood levels of mercury in children with KD and their association with disease outcome. The mercury levels demonstrated a significantly negative correlation with sodium levels (p = 0.007). However, data failed to reach a significant difference after excluding the child with blood mercury exceeding the toxic value. The findings indicate that KD patients with lower sodium concentrations had a remarkably higher proportion of intravenous immunoglobulin (IVIG) resistance (p = 0.022). Our patients who had lower mercury levels (&lt, 0.5 &mu, g/L) had more changes in bacille Calmette-Guerin. Mercury levels in 14/14 patients with coronary artery lesions and 4/4 patients with IVIG resistance were all measured to have values greater than 1 &mu, g/L (while average values showed 0.92 &mu, g/L in Asian American children). Mercury levels had no correlations with IVIG resistance or coronary artery lesion (CAL) formation (p &gt, 0.05). CAL development was more common in the incomplete group than in the complete KD group (p = 0.019). In this first report about mercury levels in KD patients, we observed that the juvenile Taiwanese had higher mercury concentration in blood compared to other populations.

Background: Kawasaki disease (KD) is the most common acute coronary vasculitis to occur in children. Although we have uncovered global DNA hypomethylation in KD, its underlying cause remains uncertain. In this study, we performed a survey of transcript levels of DNA methyltransferases and demethylases in KD patients. Materials and Methods: We recruited 145 participants for this study. The chip studies consisted of 18 KD patients that were analyzed before undergoing intravenous immunoglobulin (IVIG) treatment and at least 3 weeks after IVIG treatment, as well as 36 control subjects, using Affymetrix GeneChip® Human Transcriptome Array 2.0. An additional study of 91 subjects was performed in order to validate real-time quantitative PCR. Results: In our microarray study, the mRNA levels of DNMT1 and DNMT3A were significantly lower while TET2 was higher in acute-stage KD patients compared to the healthy controls. Through PCR validation, we observed that the expression of DNMT1 and TET2 are consistent with the Transcriptome Array 2.0 results. Furthermore, we observed significantly lower DMNT1 mRNA levels following IVIG treatment between those who developed CAL and those who did not. Conclusion: Our findings provide an evidence of DNA methyltransferases and demethylases changes and are among the first report that transient DNA hypomethylation is induced during acute inflammatory phase of Kawasaki disease.

Kawasaki disease (KD) is an acute febrile systemic vasculitis that disturbs coronary arteries. Patients' risks of adverse cardiovascular events and subclinical atherosclerosis have been found to significantly increase with polymorphisms of the human cytochrome P450. This current study aims to research the possible relationship between cytochrome P450, family 2, subfamily E and polypeptide 1 (CYP2E1) polymorphisms with KD.We selected 6 tag single-nucleotide polymorphisms (SNPs) of the CYP2E1 gene for TaqMan allelic discrimination assay in 340 KD patients and performed analysis on the clinical phenotypes and coronary artery lesions (CALs). CAL associations of tag SNPs were adjusted for age and gender in the logistic regression.The KD patients with a CC genotype of rs915906 demonstrated a greater proportion of CAL formation (P = 0.009). Furthermore, the GG genotype frequencies of rs2070676 showed a significantly greater risk for CAL formation in KD patients (P = 0.007). However, the SNPs of the CYP2E1 gene did not influence CAL formation in the participating KD patients either with or without high-dose acetylsalicylic acid. Using the expression quantitative trait locus analyses, we found that the SNPs associated with CAL formation in KD also affected CYP2E1 expression in certain cell types.This study is the first to find that the risk of CAL formation is related to CYP2E1 gene polymorphisms in KD patients.

A growing number of diseases in humans, including trauma, certain cancers, and infection, are known to be associated with l-arginine deficiency. In addition, l-arginine must be supplemented by diet during pregnancy to aid fetal development. In conditions of l-arginine depletion, T cell proliferation is impaired. We have previously shown that neonatal blood has lower l-arginine levels than adult blood, which is associated with poor neonatal lymphocyte proliferation, and that l-arginine enhances neonatal lymphocyte proliferation through an interleukin (IL)-2-independent pathway. In this study, we have further investigated how exogenous l-arginine enhances neonatal regulatory T-cells (Tregs) function in relation to IL-10 production under epigenetic regulation. Results showed that cord blood mononuclear cells (CBMCs) produced higher levels of IL-10 than adult peripheral blood mononuclear cells (PBMCs) by phytohemagglutinin stimulation but not by anti-CD3/anti-CD28 stimulation. Addition of exogenous l-arginine had no effect on transforming growth factor-β production by PBMCs or CBMCs, but enhanced IL-10 production by neonatal CD4+CD25+FoxP3+ Tregs. Further studies showed that IL-10 promoter DNA hypomethylation, rather than histone modification, corresponded to the l-arginine-induced increase in IL-10 production by neonatal CD4+ T cells. These results suggest that l-arginine modulates neonatal Tregs through the regulation of IL-10 promoter DNA methylation. l-arginine supplementation may correct the Treg function in newborns with l-arginine deficiency.