2025
Molecular characterization of Kawasaki disease subgroups using cell-free RNA profiling
Loy C, Wang H, Kim J, Shimizu C, Lenz J, Belcher E, Tremoulet A, Burns J, De Vlaminck I. Molecular characterization of Kawasaki disease subgroups using cell-free RNA profiling. Scientific Reports 2025, 15: 29799. PMID: 40813796, PMCID: PMC12354920, DOI: 10.1038/s41598-025-15843-7.Peer-Reviewed Original ResearchConceptsHeterogeneous clinical presentationKawasaki diseaseRNA profilesMolecular characterizationRNA transcript abundanceDisease subgroupsPresentation of Kawasaki diseaseClinical presentation of Kawasaki diseaseAcquired heart diseaseKawasaki disease patientsTranscript abundancePathway enrichment scoresRNA sequencingCell-free RNAEnrichment scoresKD phenotypeMitochondrial dysfunctionFebrile childrenHealthy childrenPediatric vasculitisClinical variablesClinical subgroupsDisease stratificationMolecular signaturesPlatelet activation
2024
Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease
Zhang Y, Jia C, Guo M, Chen Q, Wen Y, Wang T, Xie Y, Fan X, Gao J, Yarovinsky T, Liu R, Jiang Z, Wang M, Zhou J, Che D, Fu L, Edelson R, Gu X, Hwa J, Tang W. Platelet–Monocyte Aggregate Instigates Inflammation and Vasculopathy in Kawasaki Disease. Advanced Science 2024, 12: 2406282. PMID: 39665236, PMCID: PMC11792051, DOI: 10.1002/advs.202406282.Peer-Reviewed Original ResearchKawasaki diseaseCD14<sup>+</sup>CD16<sup>+</sup> monocytesPlatelet-monocyte aggregatesAberrant immune responseAcute febrile illnessCoronary artery aneurysmsNuclear factor-kappaBSystemic vasculitisPlatelet-monocyteProinflammatory monocytesPlatelet hyperreactivityArtery aneurysmVasculopathyFebrile illnessCytokine mediatorsHyperactive plateletsReduce inflammationPlatelet glycoproteinImmune responseInterleukin-1Platelet activationPositive feedback loopLigand 1MonocytesGrowth factorPlasma cell-free RNA signatures of inflammatory syndromes in children
Loy C, Servellita V, Sotomayor-Gonzalez A, Bliss A, Lenz J, Belcher E, Suslovic W, Nguyen J, Williams M, Oseguera M, Gardiner M, P.E.M.K.D.R.G., Group T, Choi J, Hsiao H, Wang H, Kim J, Shimizu C, Tremoulet A, Delaney M, DeBiasi R, Rostad C, Burns J, Chiu C, De Vlaminck I, Austin-Page L, Bryl A, Donofrio-Ödmann J, Ekpenyong A, Gutglass D, Herskovitz S, Ishimine P, Kanegaye J, Nguyen M, Nguyen M, Schwartz K, Ulrich S, Vayngortin T, Zimmerman E, Ang J, Rosenkranz M, Bochini J, Sykes M, Morgan L, D’Addese L, Gutierrez M. Plasma cell-free RNA signatures of inflammatory syndromes in children. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2403897121. PMID: 39240972, PMCID: PMC11406294, DOI: 10.1073/pnas.2403897121.Peer-Reviewed Original ResearchConceptsPediatric inflammatory syndromeInflammatory syndromeKawasaki diseaseMIS-CDifferential diagnosisBacterial infectionsMultisystem inflammatory syndromeUpper respiratory tractPediatric patientsInflammatory conditionsCfRNAViral infectionSyndromeMolecular diagnostic toolsRespiratory tractPlasma samplesNervous systemHospital admissionInfectionDiagnostic toolAdvanced molecular diagnostic toolDiagnosisSpecific tissuesPlasmaChildren
2023
Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children
Kim J, Shimizu C, He M, Wang H, Hoffman H, Tremoulet A, Shyy J, Burns J. Endothelial Cell Response in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children. International Journal Of Molecular Sciences 2023, 24: 12318. PMID: 37569694, PMCID: PMC10418493, DOI: 10.3390/ijms241512318.Peer-Reviewed Original ResearchConceptsKawasaki diseaseEndothelial cellsCardiovascular outcomesInflammatory syndromeWeighted gene co-expression network analysisDifferent cardiovascular outcomesMultisystem inflammatory syndromePre-treatment serumEC homeostasisEndothelial-mesenchymal transitionCultured endothelial cellsPro-survival genesClinical manifestationsHealthy controlsImmune responseNFκB pathwayCell responsesEndothelial cell responsesDiseaseGene co-expression network analysisEC responseExpression levelsSyndromeCo-expression network analysisReduced transcripts
2022
Publisher Correction: An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease
Ghosh P, Katkar G, Shimizu C, Kim J, Khandelwal S, Tremoulet A, Kanegaye J, Bocchini J, Das S, Burns J, Sahoo D. Publisher Correction: An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease. Nature Communications 2022, 13: 4729. PMID: 35953486, PMCID: PMC9372045, DOI: 10.1038/s41467-022-32479-7.Peer-Reviewed Original ResearchRNA Sequencing Reveals Beneficial Effects of Atorvastatin on Endothelial Cells in Acute Kawasaki Disease
Shimizu C, Kim J, He M, Tremoulet A, Hoffman H, Shyy J, Burns J. RNA Sequencing Reveals Beneficial Effects of Atorvastatin on Endothelial Cells in Acute Kawasaki Disease. Journal Of The American Heart Association 2022, 11: e025408. PMID: 35861833, PMCID: PMC9707837, DOI: 10.1161/jaha.122.025408.Peer-Reviewed Original ResearchConceptsKawasaki diseaseGenome-wide transcriptional changesIntravenous immunoglobulinAcute Kawasaki diseaseHuman umbilical vein ECsInflammatory cell infiltrationEndothelial cell dysfunctionTumor necrosis factorTranscriptional changesRNA sequencingKD treatmentAcute phaseMyointimal proliferationCoronary arteryCell infiltrationCultured ECsNecrosis factorCell dysfunctionKD seraInterleukin-1Recruitment pathwayResponse of ECBackground damageSerumPatientsAn Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease
Ghosh P, Katkar G, Shimizu C, Kim J, Khandelwal S, Tremoulet A, Kanegaye J, Bocchini J, Das S, Burns J, Sahoo D. An Artificial Intelligence-guided signature reveals the shared host immune response in MIS-C and Kawasaki disease. Nature Communications 2022, 13: 2687. PMID: 35577777, PMCID: PMC9110726, DOI: 10.1038/s41467-022-30357-w.Peer-Reviewed Original ResearchConceptsKawasaki diseaseHost immune responseLaboratory parametersImmune responseSARS-CoV-2 infectionInflammatory syndromeCytokine stormSerum cytokinesClinical featuresCytokine pathwaysCardiac phenotypeSyndromeGene signaturePediatric syndromesViral pandemicHeart tissueCOVID-19COVID-19 pandemicProximal pathwayDiseaseSeverityImmunopathogenesisPandemicCytokinesIllnessClinical characteristics and treatments of multi-system inflammatory syndrome in children: a systematic review.
Lee K, Li H, Lee M, Park S, Kim J, Han Y, Cho K, Ha B, Kim S, Jacob L, Koyanagi A, Shin J, Kim J, Smith L. Clinical characteristics and treatments of multi-system inflammatory syndrome in children: a systematic review. European Review For Medical And Pharmacological Sciences 2022, 26: 3342-3350. PMID: 35587087, DOI: 10.26355/eurrev_202205_28754.Peer-Reviewed Original ResearchConceptsMIS-CSevere COVID-19Kawasaki diseaseInflammatory syndromeDiagnostic criteriaMulti-system inflammatory syndromeAtypical Kawasaki diseaseAge of patientsMultisystem inflammatory syndromeAssociated with coronavirus disease 2019Indicators of inflammationIntravenous immunoglobulinLaboratory characteristicsPresenting symptomsInotropic agentsMIS-C.D-dimerCase seriesClinical characteristicsCardiac injuryGastrointestinal symptomsTroponin IEarly diagnosisIL-6Average age
2021
Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles
Jackson H, Menikou S, Hamilton S, McArdle A, Shimizu C, Galassini R, Huang H, Kim J, Tremoulet A, Thorne A, Fischer R, de Jonge M, Kuijpers T, Wright V, Burns J, Casals-Pascual C, Herberg J, Levin M, Kaforou M, On Behalf Of The Perform Consortium. Kawasaki Disease Patient Stratification and Pathway Analysis Based on Host Transcriptomic and Proteomic Profiles. International Journal Of Molecular Sciences 2021, 22: 5655. PMID: 34073389, PMCID: PMC8198135, DOI: 10.3390/ijms22115655.Peer-Reviewed Original ResearchConceptsKawasaki diseaseViral infectionHost responseKD patientsAcute inflammatory disordersAnti-bacterial responsePathway analysisBacterial patientsInflammatory disordersInflammatory responsePatient stratificationCommon triggerPatientsKD samplesHost transcriptomicsInfectionProteomic profilesOmics profilesDifferent triggersDiagnostic signatureResponseInflammationTriggersLevelsEtiologySARS-CoV-2–related MIS-C: A key to the viral and genetic causes of Kawasaki disease?
Sancho-Shimizu V, Brodin P, Cobat A, Biggs CM, Toubiana J, Lucas CL, Henrickson SE, Belot A, Haddad E, Beland K, Pujol A, Schlüter A, Planas-Serra L, Aguilera-Albesa S, Valencia-Ramos J, Rodríguez-Palmero A, Gut M, Rivière J, Colobran R, Soler-Palacin P, Rodriguez-Gallego C, De Diego R, Flores C, Alsina L, Blazquez-Gamero D, Jordan I, Keles S, Emiroglu M, Akcan O, Alkan G, Aytekin S, Gul Y, Öz Ş, Bozdemir S, Bayhan G, Kanık-Yüksek S, Parlakay A, Gülhan B, Yahşi A, Kilic A, Karbuz A, Erdeniz E, Özkan E, Orbak Z, Aydemir Ş, Celik J, Kandemir B, Aytekin G, Kapakli H, Yarar V, Yosunkaya A, Vatansev H, Aytekin C, Torun S, Nepesov S, Coskuner T, Sözeri B, Demirkol Y, Kasapcopur O, Yıldız M, Sevketoglu E, Hatipoğlu N, Özçelik T, Yesilbas O, Aydin Z, Sediva A, Klocperk A, Bloomfield M, Meyts I, Delafontaine S, Haerynck F, Hoste L, Shahrooei M, Marque L, Neves J, Novelli G, Novelli A, Aiuti A, Casari G, Bousfiha A, Almuhsen S, Sobh A, Gagro A, Bajolle F, Bonnet D, Lebon P, Lei W, Lee D, Seeleuthner Y, Zhang P, Maglorius M, Philippot Q, Pelham S, Bastard P, Zhang Q, Jouanguy E, Puel A, Herberg J, Kuijpers T, Bellos E, Kaforou M, Menikou S, Pan-Hammarström Q, Hammarström L, Abolhassani H, Bryceson Y, Condino-Neto A, Prando C, Bando S, Cavalcanti A, Fellay J, Blanchard-Rohner G, Mansouri D, Mahmoudi S, Boyarchuk O, Volokha A, Bondarenko A, Stepanovskiy Y, Mogensen T, van de Beek D, Andreakos E, Papadaki M, Tayoun A, Halwani R, Al-Mulla F, Franco J, Lau Y, Kwan M, Imai K, Okada S, Bolze A, Butte M, Hsieh E, Drolet B, Arkin L, Itan Y, Maniatis T, Arditi M, Cooper M, Schmitt E, Chakravorty S, Anderson M, Su H, Notarangelo L, Tangye S, Milner J, Levin M, Abel L, Bogunovic D, Casanova J, Zhang S. SARS-CoV-2–related MIS-C: A key to the viral and genetic causes of Kawasaki disease? Journal Of Experimental Medicine 2021, 218: e20210446. PMID: 33904890, PMCID: PMC8080850, DOI: 10.1084/jem.20210446.Peer-Reviewed Original ResearchConceptsClassic Kawasaki diseaseKawasaki diseaseSARS-CoV-2Higher COVID-19 ratesPathogenesis of MISRare inborn errorCOVID-19 ratesMonogenic IEIInflammatory syndromeViral illnessViral triggerInflammatory conditionsImmune responseEpidemiological dataInborn errorsGenetic causeWeak associationPathogenesisDiseaseIEIChildrenSyndromeIllnessInfectionImmunity
2020
Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis
Zhang Y, Wang Y, Zhang L, Xia L, Zheng M, Zeng Z, Liu Y, Yarovinsky T, Ostriker AC, Fan X, Weng K, Su M, Huang P, Martin KA, Hwa J, Tang WH. Reduced Platelet miR-223 Induction in Kawasaki Disease Leads to Severe Coronary Artery Pathology Through a miR-223/PDGFRβ Vascular Smooth Muscle Cell Axis. Circulation Research 2020, 127: 855-873. PMID: 32597702, PMCID: PMC7486265, DOI: 10.1161/circresaha.120.316951.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAnimalsBlood PlateletsCase-Control StudiesCells, CulturedChildChild, PreschoolCoronary Artery DiseaseCoronary VesselsDisease Models, AnimalFemaleHumansInfantMaleMice, Inbred C57BLMice, KnockoutMicroRNAsMucocutaneous Lymph Node SyndromeMuscle, Smooth, VascularMyocytes, Smooth MusclePlatelet ActivationProspective StudiesReceptor, Platelet-Derived Growth Factor betaSeverity of Illness IndexSignal TransductionYoung AdultConceptsSevere coronary pathologyCoronary artery pathologyKawasaki diseaseCoronary pathologyArtery pathologyMiR-223Medial damageHealthy controlsVSMC dedifferentiationHallmark of KDMiR-223 knockout miceVascular smooth muscle cell dedifferentiationSmooth muscle cell dedifferentiationPlatelet miR-223Platelet-derived miRNAsVSMC differentiationMedial elastic fibersMiR-223 levelsMuscle cell dedifferentiationPotential therapeutic strategyInhibitor imatinib mesylateVascular smooth muscle cell phenotypeSmooth muscle cell phenotypeMiR-223 mimicsUptake of platelets
2019
HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease
Shimizu C, Kim J, Eleftherohorinou H, Wright V, Hoang L, Tremoulet A, Franco A, Hibberd M, Takahashi A, Kubo M, Ito K, Tanaka T, Onouchi Y, Coin L, Levin M, Burns J, Shike H, Consortium O. HLA-C variants associated with amino acid substitutions in the peptide binding groove influence susceptibility to Kawasaki disease. Human Immunology 2019, 80: 731-738. PMID: 31122742, PMCID: PMC10793643, DOI: 10.1016/j.humimm.2019.04.020.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAmino Acid SequenceAmino Acid SubstitutionAntigen PresentationBinding SitesCohort StudiesGene FrequencyGenetic Predisposition to DiseaseGenotypeHistocompatibility TestingHLA-C AntigensHumansJapanMucocutaneous Lymph Node SyndromePeptidesPolymorphism, Single NucleotideProtein BindingProtein DomainsT-Lymphocytes, CytotoxicConceptsKawasaki diseaseCytotoxic T cellsSusceptible childrenJapanese cohortRisk A-alleleSingle cohort studyHLA class ISingle nucleotide variantsHLA-C variantsHLA-B geneCohort studyPediatric vasculitisAmino acid substitutionsT cellsKD susceptibilityHLAUnknown triggerA alleleRisk allelesClass ICohortInfluence susceptibilityAcid substitutionsNon-conservative amino acid substitutionsVasculitisA BALLOONING CARDIOVASCULAR CONDITION: REVASCULARIZATION IN A PATIENT WITH KAWASAKI DISEASE AND CORONARY ARTERY ANEURYSMS
Upadhyaya K, Remetz M. A BALLOONING CARDIOVASCULAR CONDITION: REVASCULARIZATION IN A PATIENT WITH KAWASAKI DISEASE AND CORONARY ARTERY ANEURYSMS. Journal Of The American College Of Cardiology 2019, 73: 2431. DOI: 10.1016/s0735-1097(19)33037-2.Peer-Reviewed Original Research
2018
Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers
Rypdal M, Rypdal V, Burney J, Cayan D, Bainto E, Skochko S, Tremoulet A, Creamean J, Shimizu C, Kim J, Burns J. Clustering and climate associations of Kawasaki Disease in San Diego County suggest environmental triggers. Scientific Reports 2018, 8: 16140. PMID: 30420674, PMCID: PMC6232126, DOI: 10.1038/s41598-018-33124-4.Peer-Reviewed Original ResearchConceptsKawasaki diseaseKD casesCases of KDEnvironmental triggersMore environmental triggersCertain clinical characteristicsRegional children's hospitalClinical characteristicsKD patientsChildren's HospitalDisease characteristicsSusceptible childrenHeart diseaseCommon causeDiseaseEpisodic exposurePatientsHospitalGene expression analysisSan Diego CountyGene expression patternsExpression patternsDisease incidenceTemporal clustersBifid T waves on the ECG and genetic variation in calcium channel voltage‐dependent beta 2 subunit gene (CACNB2) in acute Kawasaki disease
Oyamada J, Shimizu C, Kim J, Williams M, Png E, Hibberd M, Tremoulet A, Perry J, Burns J. Bifid T waves on the ECG and genetic variation in calcium channel voltage‐dependent beta 2 subunit gene (CACNB2) in acute Kawasaki disease. Congenital Heart Disease 2018, 14: 213-220. PMID: 30395415, DOI: 10.1111/chd.12696.Peer-Reviewed Original ResearchConceptsBifid T wavesKawasaki diseaseT-wave morphologyKD subjectsT waveIndependent cohortKD susceptibilityAcute KD subjectsAcute Kawasaki diseaseSelf-limited vasculitisSubunit geneGenetic variantsGenotype/phenotype association studiesWide association study dataGenome-wide association study dataIntracellular calcium signalingPhenotype association studiesWave morphologyAssociation study dataCalcium channel geneCommon causeCardiac repolarizationMyocardial repolarizationCardiac diseaseAbnormal repolarizationA Novel Stakeholder Engagement Approach for Patient-centered Outcomes Research
Kim K, Khodyakov D, Marie K, Taras H, Meeker D, Campos H, Ohno-Machado L. A Novel Stakeholder Engagement Approach for Patient-centered Outcomes Research. Medical Care 2018, 56: s41-s47. PMID: 30074950, PMCID: PMC6143220, DOI: 10.1097/mlr.0000000000000790.Peer-Reviewed Original ResearchConceptsClinical Data Research NetworkPatient-centered outcomes researchEngagement of patientsOutcomes research studiesConditions of focusStakeholder advisory boardPatient-centered outcomes research studiesKawasaki diseaseHeart failurePatient advocatesPatientsClinical sitesOutcomes researchSignificant differencesHealth researchCliniciansResearch NetworkResearch prioritiesSetting of prioritiesEngagement strategiesAdvisory BoardFavorable opinionObesityEngagement principlesDisease
2017
Development of quality metrics for ambulatory pediatric cardiology: Infection prevention
Johnson JN, Barrett CS, Franklin WH, Graham EM, Halnon NJ, Hattendorf BA, Krawczeski CD, McGovern JJ, O'Connor MJ, Schultz AH, Vinocur JM, Chowdhury D, Anderson JB. Development of quality metrics for ambulatory pediatric cardiology: Infection prevention. Congenital Heart Disease 2017, 12: 756-761. PMID: 28741863, DOI: 10.1111/chd.12519.Peer-Reviewed Original ResearchConceptsInfection preventionPediatric cardiologyAntibiotic prophylaxisRheumatic feverHand hygieneAdult CongenitalAmbulatory practiceRespiratory syncytial virus prophylaxisAsplenia/hyposplenismInfluenza vaccination complianceInfluenza vaccination recommendationsTetralogy of FallotQuality improvement initiativesAmbulatory pediatric cardiologyChest painInfluenza vaccinationKawasaki diseaseSecondary preventionVaccination recommendationsArterial switchCardiopulmonary bypassGreat arteriesSplenic functionVaccination compliancePreoperative method
2016
Comparative analysis of stakeholder experiences with an online approach to prioritizing patient-centered research topics
Khodyakov D, Grant S, Meeker D, Booth M, Pacheco-Santivanez N, Kim K. Comparative analysis of stakeholder experiences with an online approach to prioritizing patient-centered research topics. Journal Of The American Medical Informatics Association 2016, 24: 537-543. PMID: 28011596, PMCID: PMC7651951, DOI: 10.1093/jamia/ocw157.Peer-Reviewed Original ResearchConceptsStudy participationPatient/caregiver experienceKawasaki diseaseHeart failureRating roundsCaregivers' experiencesProfessional stakeholdersMultivariate modelConvenience samplePatientsDelphi panelCliniciansPerson meetingsResearch prioritizationSelf-reported willingnessLittle evidenceParticipants' experiencesStakeholder experiencesObesityDiseaseExperience indexPediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady
Johnson RM, Bergmann KR, Manaloor JJ, Yu X, Slaven JE, Kharbanda AB. Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady. Open Forum Infectious Diseases 2016, 3: ofw160. PMID: 27704015, PMCID: PMC5047405, DOI: 10.1093/ofid/ofw160.Peer-Reviewed Original ResearchKawasaki-like syndromeHuman immunodeficiency virusEnzyme-linked immunosorbent assayMultiplex enzyme-linked immunosorbent assayPediatric Kawasaki diseaseKawasaki diseaseAcute phase reactantsInflammatory signatureFebrile controlsKD subjectsAsymptomatic human immunodeficiency virusElevated acute phase reactantsCommon etiologic agentTumor necrosis factorSimilar physical findingsAntiretroviral therapyConvalescent phaseFebrile illnessCytokine milieuIg therapyInflamed arteriesCommon etiologyImmunodeficiency virusPhysical findingsTherapeutic responseBuilding a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes
Doan S, Maehara C, Chaparro J, Lu S, Liu R, Graham A, Berry E, Hsu C, Kanegaye J, Lloyd D, Ohno‐Machado L, Burns J, Tremoulet A, Group T. Building a Natural Language Processing Tool to Identify Patients With High Clinical Suspicion for Kawasaki Disease from Emergency Department Notes. Academic Emergency Medicine 2016, 23: 628-636. PMID: 26826020, PMCID: PMC5031359, DOI: 10.1111/acem.12925.Peer-Reviewed Original ResearchConceptsDiagnosis of KDKawasaki diseaseED notesHigh suspicionPediatric ED patientsSerious cardiac complicationsHigh clinical suspicionEmergency department patientsManual chart reviewCardiac complicationsChart reviewClinical suspicionFebrile illnessDepartment patientsED patientsElectronic health record systemsEmergency departmentClinical signsDiagnostic criteriaHealth record systemsPatientsClinical termsSuspicionDiagnosisRecord system
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