Featured Publications
Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis
Barmada A, Klein J, Ramaswamy A, Brodsky N, Jaycox J, Sheikha H, Jones K, Habet V, Campbell M, Sumida T, Kontorovich A, Bogunovic D, Oliveira C, Steele J, Hall E, Pena-Hernandez M, Monteiro V, Lucas C, Ring A, Omer S, Iwasaki A, Yildirim I, Lucas C. Cytokinopathy with aberrant cytotoxic lymphocytes and profibrotic myeloid response in SARS-CoV-2 mRNA vaccine–associated myocarditis. Science Immunology 2023, 8: eadh3455-eadh3455. PMID: 37146127, PMCID: PMC10468758, DOI: 10.1126/sciimmunol.adh3455.Peer-Reviewed Original ResearchConceptsMRNA vaccinesSARS-CoV-2 mRNA vaccinesSARS-CoV-2 mRNA vaccinationC-reactive protein levelsB-type natriuretic peptidePeripheral blood mononuclear cellsCardiac tissue inflammationDeep immune profilingSerum soluble CD163Vaccine-associated myocarditisCohort of patientsBlood mononuclear cellsCytotoxic T cellsLate gadolinium enhancementHypersensitivity myocarditisElevated troponinMRNA vaccinationImaging abnormalitiesNK cellsImmune profilingKiller cellsMyeloid responseNatriuretic peptideHumoral mechanismsInflammatory cytokinesNovel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome
Brodsky NN, Boyarchuk O, Kovalchuk T, Hariyan T, Rice A, Ji W, Khokha M, Lakhani S, Lucas CL. Novel compound heterozygous variants in NHLRC2 in a patient with FINCA syndrome. Journal Of Human Genetics 2020, 65: 911-915. PMID: 32435055, DOI: 10.1038/s10038-020-0776-0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAngiomatosisBrain NeoplasmsCardiomegalyChild, PreschoolExome SequencingFibrosisHeterozygoteHumansIntracellular Signaling Peptides and ProteinsLung DiseasesMaleModels, MolecularNeurodegenerative DiseasesPedigreePoint MutationProtein ConformationProtein DomainsSequence AlignmentSequence Homology, Amino AcidSyndromeConceptsWhole-exome sequencingNovel compound heterozygous variantsCompound heterozygous variantsUkrainian patientsClinical featuresNovel variantsNew patientsHealthy humansCompound heterozygous combinationPatientsHeterozygous variantsSyndromeFinnish childrenNHLRC2Sanger sequencingFibrosisDiseaseGnomAD databaseN-terminal thioredoxinCentral regulatorVariantsNeurodegenerationInfections in activated PI3K delta syndrome (APDS)
Brodsky NN, Lucas CL. Infections in activated PI3K delta syndrome (APDS). Current Opinion In Immunology 2021, 72: 146-157. PMID: 34052541, DOI: 10.1016/j.coi.2021.04.010.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsPI3K delta syndromeHematopoietic stem cell transplantAnti-microbial prophylaxisPI3K-delta syndromeStem cell transplantSenescent T cellsSpectrum of infectionsAdaptive immune functionAutosomal dominant disorderCell transplantImmune defectsImmunoglobulin replacementRecurrent infectionsImmunomodulatory agentsTherapy optionsT cellsImmune functionInfection susceptibilityInborn errorsDominant disorderInfectionLymphadenopathyPatientsFunction mutationsImmunodeficiencyMultisystem Inflammatory Syndrome in Children: Host Immunologic Responses
Mazer M, Bulut Y, Brodsky N, Lam F, Sturgill J, Miles S, Shein S, Carroll C, Remy K, Section O. Multisystem Inflammatory Syndrome in Children: Host Immunologic Responses. Pediatric Critical Care Medicine 2022, 23: 315-320. PMID: 35050932, PMCID: PMC9058188, DOI: 10.1097/pcc.0000000000002897.Peer-Reviewed Original ResearchThe Mystery of MIS-C Post-SARS-CoV-2 Infection
Brodsky NN, Ramaswamy A, Lucas CL. The Mystery of MIS-C Post-SARS-CoV-2 Infection. Trends In Microbiology 2020, 28: 956-958. PMID: 33190685, PMCID: PMC7556780, DOI: 10.1016/j.tim.2020.10.004.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsSevere acute respiratory syndrome coronavirus 2Acute respiratory syndrome coronavirus 2SARS-CoV-2 infectionRespiratory syndrome coronavirus 2Multisystem inflammatory syndromeCoronavirus disease 2019 (COVID-19) pandemicSyndrome coronavirus 2Life-threatening illnessDisease 2019 pandemicImmune driversInflammatory syndromeCoronavirus 2Enigmatic diseaseImportant new studiesChildrenNew studiesUnique effectsSyndromeIllnessInfectionDisease
2022
A retrospective cohort analysis of the Yale pediatric genomics discovery program
Al‐Ali S, Jeffries L, Faustino EVS, Ji W, Mis E, Konstantino M, Zerillo C, Jiang Y, Spencer‐Manzon M, Bale A, Zhang H, McGlynn J, McGrath JM, Tremblay T, Brodsky NN, Lucas CL, Pierce R, Deniz E, Khokha MK, Lakhani SA. A retrospective cohort analysis of the Yale pediatric genomics discovery program. American Journal Of Medical Genetics Part A 2022, 188: 2869-2878. PMID: 35899841, PMCID: PMC9474639, DOI: 10.1002/ajmg.a.62918.Peer-Reviewed Original ResearchConceptsRetrospective cohort analysisNext-generation sequencingCohort analysisSystem abnormalitiesImmune system abnormalitiesCardiovascular system abnormalitiesFunctional molecular analysesNovel genesPrecise molecular diagnosisClinical characteristicsFurther genetic evaluationDiscovery programsComplex patientsMultisystem diseaseDisease genesPediatric providersRare genetic diseaseNew diagnosisPhenotype relationshipsPatientsGenetic diseasesMolecular analysisDiagnosisParticipant demographicsNGS results
2007
STAT3 Mutations in the Hyper-IgE Syndrome
Holland S, DeLeo F, Elloumi H, Hsu A, Uzel G, Brodsky N, Freeman A, Demidowich A, Davis J, Turner M, Anderson V, Darnell D, Welch P, Kuhns D, Frucht D, Malech H, Gallin J, Kobayashi S, Whitney A, Voyich J, Musser J, Woellner C, Schäffer A, Puck J, Grimbacher B. STAT3 Mutations in the Hyper-IgE Syndrome. New England Journal Of Medicine 2007, 357: 1608-1619. PMID: 17881745, DOI: 10.1056/nejmoa073687.Peer-Reviewed Original ResearchConceptsSrc homology 2Hyper-IgE syndromeIn-frame deletionMononuclear cellsIncreased innate immune responseInterleukin-6Tumor necrosis factor-alpha levelsElevated serum IgE levelsLevels of monocyte chemoattractant protein-1Sporadic casesIn vitro culture of mononuclear cellsMonocyte chemoattractant protein-1Innate immune responseInterleukin-6 signalingSerum IgE levelsLevels of cytokinesDisorders of immunityCultures of mononuclear cellsDNA bindingProinflammatory gene transcriptionDiscrete mutationsChemoattractant protein-1Missense mutationsSTAT3 mutationsPresence of interleukin-6