Intravenous immunoglobulin for the treatment of Kawasaki disease.
Ontology highlight
ABSTRACT:
SUBMITTER: Broderick C
PROVIDER: S-EPMC9875364 | biostudies-literature | 2023 Jan
REPOSITORIES: biostudies-literature
Publications
Intravenous immunoglobulin for the treatment of Kawasaki disease.
Broderick Cathryn C Kobayashi Shinobu S Suto Maiko M Ito Shuichi S Kobayashi Tohru T
The Cochrane database of systematic reviews 20230125
<h4>Background</h4>Kawasaki disease (KD) is an acute systemic vasculitis (inflammation of the blood vessels) that mainly affects children. Symptoms include fever, chapped lips, strawberry tongue, red eyes (bulbar conjunctival injection), rash, redness, swollen hands and feet or skin peeling; and enlarged cervical lymph nodes. High fevers and systemic inflammation characterise the acute phase. Inflammation of the coronary arteries causes the most serious complication of the disease, coronary arte ...[more]
Similar Datasets
Project description:ObjectiveTo describe the clinical course and outcome of 10 patients with Kawasaki disease (KD) treated with a calcineurin inhibitor after failing to respond to multiple therapies.Study designDemographic and clinical data were prospectively collected using standardized case report forms. T-cell phenotypes were determined by flow cytometry, and KD risk alleles in ITPKC (rs28493229), CASP3 (rs72689236), and FCGR2A (rs1801274) were genotyped.ResultsIntravenous followed by oral therapy with cyclosporine (CSA) or oral tacrolimus was well tolerated and resulted in defervescence and resolution of inflammation in all 10 patients. There were no serious adverse events, and a standardized treatment protocol was developed based on our experiences with this patient population. Analysis of T-cell phenotype by flow cytometry in 2 subjects showed a decrease in circulating activated CD8(+) and CD4(+) T effector memory cells after treatment with CSA. However, suppression of regulatory T-cells was not seen, suggesting targeting of specific, proinflammatory T-cell compartments by CSA.ConclusionTreatment of refractory KD with a calcineurin inhibitor appears to be a safe and effective approach that achieves rapid control of inflammation associated with clinical improvement.
| S-EPMC3613150 | biostudies-literature
Project description:Identifying the causes of high fever syndromes such as Kawasaki disease (KD) remains challenging. To investigate pathogen exposure signatures in suspected pathogen-mediated diseases such as KD, we performed immunoglobulin (Ig) profiling using a next-generation sequencing method. After intravenous Ig (IVIG) treatment, we observed disappearance of clonally expanded IgM clonotypes, which were dominantly observed in acute-phase patients. The complementary-determining region 3 (CDR3) sequences of dominant IgM clonotypes in acute-phase patients were commonly observed in other Ig isotypes. In acute-phase KD patients, we identified 32 unique IgM CDR3 clonotypes shared in three or more cases. Furthermore, before the IVIG treatment, the sums of dominant IgM clonotypes in IVIG-resistant KD patients were significantly higher than those of IVIG-sensitive KD patients. Collectively, we demonstrate a novel approach for identifying certain Ig clonotypes for potentially interacting with pathogens involved in KD; this approach could be applied for a wide variety of fever-causing diseases of unknown origin.
| S-EPMC6048982 | biostudies-literature
Project description:ObjectiveKawasaki disease (KD), response to intravenous immunoglobulin (IVIG) therapy, and associated coronary artery disease progression have been associated with genetic polymorphisms in Fc gamma receptor (FcγR) genes. However, it is not known whether the existing gene copy number (GCN) variability relates to KD treatment response, susceptibility, or associated sequelae.MethodsThe copy number of individuals with KD (n=510) and their family members (n=808) for three variable FcγRs was assessed using pyrosequencing. We performed the transmission disequilibrium test to examine the association of GCN for FcγRs (FcγR2C, FcγR3A, and FcγR3B) with susceptibility and used logistic regression models to determine its association with IVIG treatment outcomes.ResultsFcγR2C and FcγR3B GCN were significantly associated with KD susceptibility. IVIG response was associated with GCN variations of FcγR3B in Whites and FcγR2C in Hispanics, and gene risk score based on single nucleotide polymorphism and GCN in FcγRs were significantly different between IVIG responders and nonresponders among Whites. We found no significant associations between coronary artery disease and any of the FcγR copy numbers.ConclusionGCN of FcγR2C and FcγR3B influences IVIG treatment response and predisposes individuals to KD, providing potential insights into understanding the mechanism of the FcγR gene family in the IVIG pathway.
| S-EPMC4400828 | biostudies-literature
Project description:IntroductionKawasaki disease (KD) is a diffuse vasculitis in children. Response to high dose intravenous gamma globulin (IVIG), the primary treatment, varies according to genetic background. We sought to identify genetic loci, which associate with treatment response using whole genome sequencing (WGS).MethodWe performed WGS in 472 KD patients with 305 IVIG responders and 167 non-responders defined by AHA clinical criteria. We conducted logistic regression models to test additive genetic effect in the entire cohort and in four subgroups defined by ancestry information markers (Whites, African Americans, Asians, and Hispanics). We performed functional mapping and annotation using FUMA to examine genetic variants that are potentially involved IVIG non-response. Further, we conducted SNP-set [Sequence] Kernel Association Test (SKAT) for all rare and common variants.ResultsOf the 43,288,336 SNPs (23,660,970 in intergenic regions, 16,764,594 in introns and 556,814 in the exons) identified, the top ten hits associated with IVIG non-response were in FANK1, MAP2K3:KCNJ12, CA10, FRG1DP, CWH43 regions. When analyzed separately in ancestry-based racial subgroups, SNPs in several novel genes were associated. A total of 23 possible causal genes were pinpointed by positional and chromatin mapping. SKAT analysis demonstrated association in the entire MANIA2, EDN1, SFMBT2, and PPP2R5E genes and segments of CSMD2, LINC01317, HIVEPI, HSP90AB1, and TTLL11 genes.ConclusionsThis WGS study identified multiple predominantly novel understudied genes associated with IVIG response. These data can serve to inform regarding pathogenesis of KD, as well as lay ground work for developing treatment response predictors.
| S-EPMC10800400 | biostudies-literature
Project description:Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause. The low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) gene was reported to be involved in the susceptibility of KD. DNA methylation is one of the epigenetic mechanisms that control gene expression; thus, we hypothesized that methylation status of CpG islands in FCGR2A promoter associates with the susceptibility and therapeutic outcomes of Kawasaki disease. In this study, 36 KD patients and 24 healthy subjects from out-patient clinic were recruited. Eleven potential methylation sites within the targeted promoter region of FCGR2A were selected for investigation. We marked the eleven methylation sites from A to K. Our results indicated that methylation at the CpG sites G, H, and J associated with the risk of KD. CpG sites B, C, E, F, H, J, and K were found to associate with the outcomes of IVIG treatment. In addition, CpG sites G, J, and K were predicted as transcription factors binding sites for NF-kB, Myc-Max, and SP2, respectively. Our study reported a significant association among the promoter methylation of FCGR2A, susceptibility of KD, and the therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter should be an important marker for optimizing IVIG therapy.
| S-EPMC4451985 | biostudies-literature
Project description:In this study, we compared global gene expressions between pre- and post- intravenous immunoglobulin (IVIG) administration in nineteen Kawasaki disease (KD) patients. Peripheral blood mononuclear cells (PBMCs) obtained from nineteen patients before and after IVIG treatment was extracted using a PAXgene blood RNA isolation kit. Amplified cRNAs of each patient were analyzed using with Agilent Whole Human Genome Microarray 4x44K G4112F array.
2017-09-19 | GSE73577 | GEO
Project description:ObjectivesTo explore the increased incidence of intravenous immunoglobulin- (IVIG) resistance among San Diego County patients with Kawasaki disease (KD) in 2006 and to evaluate a scoring system to predict IVIG-resistant patients with KD.Study designWe performed a retrospective review of patients with KD treated within 10 days of fever onset. With multivariate analysis, independent predictors of IVIG-resistance were combined into a scoring system.ResultsIn 2006, 38.3% of patients with KD in San Diego County were IVIG-resistant, a significant increase over previous years. IVIG-resistance was not associated with a particular brand or lot of IVIG. Resistant patients were diagnosed earlier, had higher percent bands, and higher concentrations of C-reactive protein, alanine aminotransferase, and gamma-glutamyl transferase. They also had lower platelet counts and age-adjusted hemoglobin concentrations and were more likely to have aneurysms (P = .0008). A scoring system developed to predict IVIG-resistant patients using illness day, percent bands, gamma-glutamyl transferase, and age-adjusted hemoglobin had a sensitivity of 73.3% and specificity of 61.9%.ConclusionsAn unexplained increase in IVIG-resistance was noted among patients with KD in San Diego County in 2006. Scoring systems based on demographic and laboratory data were insufficiently accurate to be clinically useful in our ethnically diverse population.
| S-EPMC2526555 | biostudies-literature
Project description:ObjectiveTo investigate the predictive value of thrombospondin-2 (TSP-2) in assessing the response to intravenous immunoglobulin (IVIG) in children with acute Kawasaki disease (KD).MethodsThis was a cohort study with controls. 71 children with KD were recruited as the case group, including IVIG non-responder (n=17) and IVIG responder (n=54), and healthy children (n=27) and febrile children (n=30) were used as control groups. ELISA was used to measure plasma TSP-2 and TSP-1 levels. The rank-sum test was used to compare groups of non-normally distributed data. Predictive value was evaluated through the receiver operating characteristic (ROC) curve.ResultsCompared with the control groups, the plasma TSP-2 levels in acute KD were significantly elevated (TSP-2: 31.00 (24.02, 39.28) vs 21.93 (17.00, 24.73) vs 16.23 (14.00, 19.64) ng/mL, P<0.001). The plasma TSP-2 level in the IVIG non-responder was significantly higher than the responder group (37.58 (31.86, 43.98) vs 27.84 (21.88, 33.48) ng/mL, P=0.002). When using an ROC curve to analyse the predictive effect of TSP-2 on non-responsiveness to IVIG treatment, the area under the curve was 0.752 (0.630, 0.875) (P=0.002). When the cut-off value for TSP-2 was 31.50 ng/mL, the sensitivity was 82.35%, the specificity was 64.81%.ConclusionThe plasma TSP-2 level was elevated in acute KD and it might be a novel predictor for IVIG resistance, which could help guide clinicians to choose individualised initial therapeutic regimens.
| S-EPMC5842996 | biostudies-literature
Project description:BackgroundWe aimed to assess the efficacy of different initial intravenous immunoglobulin (IVIG) regimens in Kawasaki disease (KD) patients to find more cost-effective therapy options.MethodsA multicenter, open-label, blind-endpoint randomized controlled trial was conducted from January 2014 to December 2015. Patients with KD, within 10 days of illness, were randomly assigned to receive different IVIG regimens (Group A, 2 g/kg once; Group B, 1 g/kg for 2 consecutive days; Group C, 1 g/kg once) and aspirin 30mg/kg/d. Primary outcomes included hours to defervescence and development of coronary artery lesions during the study period. Major secondary outcomes included total fever days, total dose of IVIG, changes of laboratory data, length of stay, and hospitalization expenses. (ClinicalTrials.gov: NCT02439996).ResultsA total of 404 patients underwent randomization. No difference was found in the outcomes of defervescence among three groups at 6, 12, 24, and 36 hours after completion of initial IVIG infusion. There were no differences in the incidence of coronary artery lesions during the study period (at week 2, month 1, month 3, and month 6 of illness), changes of laboratory data, total fever days, and length of stay. Group C patients had the lowest total dose of IVIG (mean: 1.2 vs 2.2 vs 2.1 g/kg; P < 0.001) and hospitalization expenses (mean: 8443.8 vs 10798.4 vs 11011.4 Chinese Yuan; P < 0.001) than other two groups.ConclusionsA single dose of 1g/kg IVIG is a low-cost treatment with the same efficacy as 2 g/kg IVIG and can be an option for the initial therapy of KD patients.
| S-EPMC8362187 | biostudies-literature
Project description:Intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients comprise at least 20% of treated patients and are at high risk for coronary artery abnormalities. If identified early in the course of the disease, such patients may benefit from additional anti-inflammatory therapy. The aim of this study was to compare the transcript abundance between IVIG resistant and -responsive KD patients, to identify biomarkers that might differentiate between these two groups and to generate new targets for therapies in IVIG resistant KD patients. We compared the transcript abundance profiles of whole-blood RNA on Agilent arrays from acute and convalescent KD subjects and age-similar, healthy controls. KD subjects were stratified as IVIG resistant or -responsive based on response to initial IVIG therapy. Transcript abundance was higher for IL-1 pathway genes (IL-1 receptor, interleukin receptor associated kinase, p38 mitogen-activated protein kinase), and MMP-8. These findings point to candidate biomarkers that may predict IVIG resistance in acute KD patients. The results also underscore the importance of the IL-1 pathway as a mediator of inflammation in KD and suggest that IL-1 or its receptor may be reasonable targets for therapy, particularly for IVIG resistant patients.
| S-EPMC2929310 | biostudies-literature