Pathogenetic determinants in Kawasaki disease: the haematological point of view

Principe, Domenico Del; Pietraforte, Donatella; Gambardella, Lucrezia; Marchesi, Alessandra; Jacobis, Isabella Tarissi De; Villani, Alberto; Malorni, Walter; Straface, Elisabetta

doi:10.1111/jcmm.12992

Cited by 34 publications

(27 citation statements)

References 63 publications

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“…Del et al [ 8 ] suggested that the formation of heterotypic platelet–leucocyte aggregates, which is dependent on platelet activation, and leucocyte–RBC–platelet aggregates could at least partially be associated with the release of pro-aggregating factors (e.g., arachidonate) and/or with changes in the expression of molecules on the cell surface, including P-selectin. This crosstalk between activated platelets and leucocytes operates through several systems, including the interaction of P-selectin with P-selectin glycoprotein ligand-1 (PSGL-1).…”

Section: Discussionmentioning

confidence: 99%

Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases

Chen

Tang

et al. 2018

Eur J Pediatr

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The purpose of this study was to identify the clinical features and laboratory factors that are predictive of intravenous immunoglobulin (IVIG)-resistant Kawasaki disease. Multiple databases were searched for relevant studies on IVIG-resistant Kawasaki disease published from January 2002 to April 2017. Eligible studies were retrieved by manual review of the references. Stata 12 was used for the meta-analysis. Weighted mean differences and odds ratios with 95% confidence intervals were calculated for several indices. Twenty-eight studies involving 26,260 patients comprising 4442 IVIG-resistant Kawasaki disease patients and 21,818 IVIG-sensitive Kawasaki disease patients were included. The meta-analysis showed that the erythrocyte sedimentation rate (ESR) in the IVIG-resistant group was significantly higher than that in the IVIG-sensitive group, and that platelet count and hemoglobin levels were significantly lower in the IVIG-resistant group. The patients with oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, polymorphous rash, and initial administration of IVIG ≤ 4.0 days after the onset of symptoms were more likely to be IVIG resistant.Conclusion: The initial administration of IVIG ≤ 4.0 days after the onset of symptoms increased ESR and decreased hemoglobin and platelet counts, oral mucosa alterations, cervical lymphadenopathy, swelling of the extremities, and polymorphous rash and are the risk factors for IVIG-resistant Kawasaki disease. What is Known: • Recent reports on this topic are about aspartate aminotransferase (AST), alanine aminotransferase (ALT), gammaglutamyl transferase, total bilirubin, white blood cells, platelets, erythrocyte sedimentation rate (ESR), polymorphonuclear leukocytes (PMN), C-reactive protein (CRP), pro-brain natriuretic peptide (BNP), albumin, and sodium as the risk factors in the IVIG-resistant Kawasaki disease; however, no studies have been published on clinical features as predictors of IVIG resistance. What is New: • This meta-analysis identified the clinical features, the initial administration of IVIG ≤ 4.0 days after the onset of symptoms, and much more comprehensive laboratory indicators, such as hemoglobin, as predictors of IVIG-resistant Kawasaki disease. Electronic supplementary materialThe online version of this article (10.1007/s00431-018-3182-2) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases

Chen

Tang

et al. 2018

Eur J Pediatr

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“…Therefore, KD is the major cause of acquired heart disease in children in developed countries [ 13 ]. The etiopathogenesis of KD may be attributed to the combined effects of genetics, immunity, and infection [ 14 ]. Although the exact etiology of KD is still unknown, predicting KD is possible with molecular markers [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Multiomics analyses identified epigenetic modulation of the S100A gene family in Kawasaki disease and their significant involvement in neutrophil transendothelial migration

et al. 2018

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BackgroundKawasaki disease (KD) is a prevalent pediatric disease worldwide and can cause coronary artery aneurysm as a severe complication. Typically, DNA methylation is thought to repress the expression of nearby genes. However, the cases in which DNA methylation promotes gene expression have been reported. In addition, globally, to what extent DNA methylation affects gene expression and how it contributes to the pathogenesis of KD are not yet well understood.MethodsTo address these important biological questions, we enrolled subjects, collected DNA and RNA samples from the subjects’ total white blood cells, and performed DNA methylation (M450K) and gene expression (HTA 2.0) microarray assays.ResultsBy analyzing the variation ratios of CpG beta values (methylation percentage) and gene expression intensities, we first concluded that the CpG markers close (− 1500 bp to + 500 bp) to the transcription start sites had higher variation ratios, reflecting significant regulation capacities. Next, we observed that, globally speaking, gene expression was modestly negatively correlated (correlation rho ≈ − 0.2) with the DNA methylation status of both upstream and downstream CpG markers in the promoter region. Third, we found that specific CpG markers were hypo-methylated in disease samples compared with healthy samples and hyper-methylated in convalescent samples compared with disease samples, promoting and repressing S100A genes’ expressions, respectively. Finally, using an in vitro cell model, we demonstrated that S100A family proteins enhanced leukocyte transendothelial migration in KD.ConclusionsThis is the first study to integrate genome-wide DNA methylation with gene expression assays in KD and showed that the S100A family plays important roles in the pathogenesis of KD.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0557-1) contains supplementary material, which is available to authorized users.

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“…Although the clinical features, diagnosis and treatment of KD are well established, its pathogenesis has not been identified yet. Several lines of evidence suggest that an interplay between microbial infection and genetic predisposition serve a role in the development of the disease ( 5 – 7 ).…”

Section: Introductionmentioning

confidence: 99%

Identification of differentially expressed microRNAs in acute Kawasaki disease

et al. 2017

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The present study used microarray analysis to screen the plasma expression of microRNAs (miRNAs) in patients with acute Kawasaki disease (KD) and aimed to explore the pathogenesis of KD. Plasma was collected from children with acute KD (n=6) and from healthy control children (n=6). Total RNA was extracted and differential miRNA expression between the two groups was determined. Differentially expressed miRNAs were validated using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in an independent cohort (n=8). Target genes of the differentially expressed miRNAs were predicted and analyzed for gene ontology term enrichment and Kyoto Encyclopedia of Genes and Genomes pathways. miRNA microarray analysis revealed that seven miRNAs (miRs) were significantly upregulated (hsa-let-7b-5p, hsa-miR-223-3p, hsa-miR-4485, hsa-miR-4644, hsa-miR-4800-5p, hsa-miR-6510-5p and hsa-miR-765) and three were significantly downregulated (hsa-miR-33b-3p, hsa-miR-4443 and hsa-miR-4515) in acute KD compared with the healthy controls. hsa-miR-223-3p expression levels detected by RT-qPCR were consistent with the microarray results. A total of 62 target genes of hsa-miR-223-3p were predicted. In total, 10 differentially expressed miRNAs were identified in acute KD, of which hsa-miR-223-3p was verified by RT-qPCR.

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Pathogenetic determinants in Kawasaki disease: the haematological point of view

Cited by 34 publications

References 63 publications

Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases

Predictors of intravenous immunoglobulin-resistant Kawasaki disease in children: a meta-analysis of 4442 cases

Multiomics analyses identified epigenetic modulation of the S100A gene family in Kawasaki disease and their significant involvement in neutrophil transendothelial migration

Identification of differentially expressed microRNAs in acute Kawasaki disease

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