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-19Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K
Lucas CL, Zhang Y, Venida A, Wang Y, Hughes J, McElwee J, Butrick M, Matthews H, Price S, Biancalana M, Wang X, Richards M, Pozos T, Barlan I, Ozen A, Rao VK, Su HC, Lenardo MJ. Heterozygous splice mutation in PIK3R1 causes human immunodeficiency with lymphoproliferation due to dominant activation of PI3K. Journal Of Experimental Medicine 2014, 211: 2537-2547. PMID: 25488983, PMCID: PMC4267241, DOI: 10.1084/jem.20141759.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAlternative SplicingAntibody FormationBase SequenceCatalytic DomainCD8-Positive T-LymphocytesCell DifferentiationChild, PreschoolClass Ia Phosphatidylinositol 3-KinaseEnzyme ActivationExonsFemaleGenes, DominantHeterozygoteHumansImmunologic Deficiency SyndromesLymphoproliferative DisordersMaleMolecular Sequence DataMutationPedigreePhosphatidylinositol 3-KinasesProtein Structure, TertiarySequence DeletionSignal TransductionTelomereTOR Serine-Threonine KinasesConceptsT cellsPI3KPI3K subunitsSenescent T cellsRecurrent sinopulmonary infectionsHeterozygous splice site mutationSplice site mutationEffector cellsPeripheral bloodSinopulmonary infectionsHuman immunodeficiencyHeterozygous splice mutationsImmunodeficiency diseaseHealthy subjectsUnique disorderHeterozygous mutationsClass IaPatient cellsProminent expansionK subunitLymphoproliferationPatientsSimilar diseasesShort telomeresDisease
2021
Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients
Hashem H, Bucciol G, Ozen S, Unal S, Bozkaya IO, Akarsu N, Taskinen M, Koskenvuo M, Saarela J, Dimitrova D, Hickstein DD, Hsu AP, Holland SM, Krance R, Sasa G, Kumar AR, Müller I, de Sousa MA, Delafontaine S, Moens L, Babor F, Barzaghi F, Cicalese MP, Bredius R, van Montfrans J, Baretta V, Cesaro S, Stepensky P, Benedicte N, Moshous D, Le Guenno G, Boutboul D, Dalal J, Brooks JP, Dokmeci E, Dara J, Lucas CL, Hambleton S, Wilson K, Jolles S, Koc Y, Güngör T, Schnider C, Candotti F, Steinmann S, Schulz A, Chambers C, Hershfield M, Ombrello A, Kanakry JA, Meyts I. Hematopoietic Cell Transplantation Cures Adenosine Deaminase 2 Deficiency: Report on 30 Patients. Journal Of Clinical Immunology 2021, 41: 1633-1647. PMID: 34324127, PMCID: PMC8452581, DOI: 10.1007/s10875-021-01098-0.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine DeaminaseAdolescentAdultAgammaglobulinemiaBone Marrow Failure DisordersChildChild, PreschoolFemaleGraft vs Host DiseaseHematopoietic Stem Cell TransplantationHumansIntercellular Signaling Peptides and ProteinsKaplan-Meier EstimateMaleRetrospective StudiesSevere Combined ImmunodeficiencyTreatment OutcomeYoung AdultConceptsHematopoietic cell transplantationBone marrow failureImmune cytopeniasOverall survivalRefractory cytopeniaGVHD-free relapse-free survivalOutcomes of HCTNecrosis factor blockadeNew vascular eventsRelapse-free survivalTreatment of choiceAdenosine deaminase 2ADA2 enzyme activityInherited inborn errorFinal transplantVascular eventsMedian agePrimary outcomeDADA2 patientsRetrospective studyCell transplantationImmunological phenotypeDefinitive cureEffective treatmentCytopenias
2020
Novel 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 regulatorVariantsNeurodegeneration
2017
Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib
Rao VK, Webster S, Dalm VASH, Šedivá A, van Hagen PM, Holland S, Rosenzweig SD, Christ AD, Sloth B, Cabanski M, Joshi AD, de Buck S, Doucet J, Guerini D, Kalis C, Pylvaenaeinen I, Soldermann N, Kashyap A, Uzel G, Lenardo MJ, Patel DD, Lucas CL, Burkhart C. Effective “activated PI3Kδ syndrome”–targeted therapy with the PI3Kδ inhibitor leniolisib. Blood 2017, 130: 2307-2316. PMID: 28972011, PMCID: PMC5701526, DOI: 10.1182/blood-2017-08-801191.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChemokinesChildChild, PreschoolClass I Phosphatidylinositol 3-KinasesDemographyDose-Response Relationship, DrugFemaleHumansImmunoglobulin MImmunologic Deficiency SyndromesInfantLymph NodesLymphocyte ActivationMaleMolecular Targeted TherapyMutationOrgan SizePhenotypePrimary Immunodeficiency DiseasesProtein Kinase InhibitorsPyridinesPyrimidinesRatsSpleenT-LymphocytesTOR Serine-Threonine KinasesTransfectionConceptsImmune dysregulationT cellsB cellsElevated serum immunoglobulin MPI3K/Akt pathway activityDose-escalation studyLymph node sizeSenescent T cellsWeeks of treatmentDose-dependent suppressionTransitional B cellsTumor necrosis factorDose-dependent reductionPrecision medicine therapiesSerum immunoglobulin MNaive B cellsT cell blastsAkt pathway activityAPDS patientsPI3Kδ pathwayInflammatory markersPD-1Clinical parametersSpleen volumeImmune deficiency