Featured Publications
Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19
Sparks R, Lau W, Liu C, Han K, Vrindten K, Sun G, Cox M, Andrews S, Bansal N, Failla L, Manischewitz J, Grubbs G, King L, Koroleva G, Leimenstoll S, Snow L, Chen J, Tang J, Mukherjee A, Sellers B, Apps R, McDermott A, Martins A, Bloch E, Golding H, Khurana S, Tsang J. Influenza vaccination reveals sex dimorphic imprints of prior mild COVID-19. Nature 2023, 614: 752-761. PMID: 36599369, PMCID: PMC10481789, DOI: 10.1038/s41586-022-05670-5.Peer-Reviewed Original ResearchConceptsMild COVID-19Control individualsInnate immune genesInfluenza vaccinationCOVID-19Day 28Day 1Viral infectionNon-hospitalized COVID-19Baseline immune statusAcute viral infectionSex-matched control individualsMemory-like CD8IL-15 responsesIL-15 stimulationSex-dimorphic effectsToll-like receptorsFuture immune responseHealthy control individualsImmune genesSystems immunology approachT-cell activation signaturesHealthy male individualsMale individualsMore IFNγBroad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus
Kotliarov Y, Sparks R, Martins A, Mulè M, Lu Y, Goswami M, Kardava L, Banchereau R, Pascual V, Biancotto A, Chen J, Schwartzberg P, Bansal N, Liu C, Cheung F, Moir S, Tsang J. Broad immune activation underlies shared set point signatures for vaccine responsiveness in healthy individuals and disease activity in patients with lupus. Nature Medicine 2020, 26: 618-629. PMID: 32094927, PMCID: PMC8392163, DOI: 10.1038/s41591-020-0769-8.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAdolescentAdultAgedAged, 80 and overAntibody FormationB-LymphocytesChildChild, PreschoolCohort StudiesFemaleGene Expression ProfilingHumansInfluenza VaccinesInfluenza, HumanLupus Erythematosus, SystemicMaleMiddle AgedTranscriptomeVaccinationYellow FeverYellow Fever VaccineYoung AdultConceptsDisease activityVaccine responsivenessAutoimmune disease activityBlood transcriptional signaturesYellow fever vaccinationSystemic lupus erythematosusClinical quiescenceFever vaccinationLupus erythematosusCancer immunotherapyBaseline predictorsDisease outcomeHealthy subjectsImmune responseI IFNHealthy individualsVaccinationTranscriptional signatureImmune variationBaseline statePatientsExtent of activationBiological basisSurface proteinsInfection responseSystematic Analysis of Cell-to-Cell Expression Variation of T Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations
Lu Y, Biancotto A, Cheung F, Remmers E, Shah N, McCoy J, Tsang J. Systematic Analysis of Cell-to-Cell Expression Variation of T Lymphocytes in a Human Cohort Identifies Aging and Genetic Associations. Immunity 2016, 45: 1162-1175. PMID: 27851916, PMCID: PMC6532399, DOI: 10.1016/j.immuni.2016.10.025.Peer-Reviewed Original ResearchConceptsExpression variationDisease-associated genetic polymorphismsSingle-cell dataPrimary cell populationsCell populationsOrganismal levelFunctional associationDisease susceptibilityGenetic associationFlow cytometry dataCytometry dataGenetic polymorphismsHuman cohortsFlow cytometryCellsHigh-dimensional flow cytometryCell subpopulationsImportant rolePrevalent featureProteinPhenotypeSystematic analysisMultiple baseline measurementsPolymorphismPopulationGlobal Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses
Tsang J, Schwartzberg P, Kotliarov Y, Biancotto A, Xie Z, Germain R, Wang E, Olnes M, Narayanan M, Golding H, Moir S, Dickler H, Perl S, Cheung F, Center T, Consortium T, Obermoser G, Chaussabel D, Palucka K, Chen J, Fuchs J, Ho J, Khurana S, King L, Langweiler M, Liu H, Manischewitz J, Pos Z, Posada J, Schum P, Shi R, Valdez J, Wang W, Zhou H, Kastner D, Marincola F, McCoy J, Trinchieri G, Young N. Global Analyses of Human Immune Variation Reveal Baseline Predictors of Postvaccination Responses. Cell 2014, 157: 499-513. PMID: 24725414, PMCID: PMC4139290, DOI: 10.1016/j.cell.2014.03.031.Peer-Reviewed Original ResearchConceptsPre-existing antibody titersPostvaccination antibody responsePeripheral blood mononuclear cell transcriptomeB cell responsesBaseline time pointPostvaccination responsesInfluenza vaccinationImmune monitoringSerum titersAntibody titersAntibody responseBaseline predictorsBaseline differencesImmune parametersHuman immunityCell responsesSubpopulation frequenciesTime pointsCell populationsIntra-individual variationVaccinationTiters
2023
Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine
Cheung F, Apps R, Dropulic L, Kotliarov Y, Chen J, Jordan T, Langweiler M, Candia J, Biancotto A, Han K, Rachmaninoff N, Pietz H, Wang K, Tsang J, Cohen J. Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine. ELife 2023, 12: e80652. PMID: 36648132, PMCID: PMC9844983, DOI: 10.7554/elife.80652.Peer-Reviewed Original ResearchConceptsEarly innate responseVaccine recipientsPrior exposureInnate responseType I interferon signatureInfectious diseasesSeronegative vaccine recipientsType I IFN responseEarly antiviral responseNational InstituteInnate immune responseSystems immunology approachI IFN responseAdaptive immune phenotypesIntramural Research ProgramInterferon signatureAntibody titersVaccine trialsImmune phenotypeVirus vaccineNaive womenImmune responseSanofi PasteurDay 1Herpesvirus vaccine
2021
Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential
Rogers D, Sood A, Wang H, van Beek J, Rademaker T, Artusa P, Schneider C, Shen C, Wong D, Bhagrath A, Lebel M, Condotta S, Richer M, Martins A, Tsang J, Barreiro L, François P, Langlais D, Melichar H, Textor J, Mandl J. Pre-existing chromatin accessibility and gene expression differences among naive CD4+ T cells influence effector potential. Cell Reports 2021, 37: 110064. PMID: 34852223, DOI: 10.1016/j.celrep.2021.110064.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingGene expression differencesCell receptor signalingChromatin accessibilityLineage choiceTCR signal strengthCell chromatinTranscriptional differencesRNA sequencingExpression differencesReceptor signalingLandscape differencesEffector potentialEffector lineagesThymic developmentCellsNaive CD4Self-peptide MHCChromatinCognate antigenLineagesGenesSignalingTCR interactionsKey driversTime-resolved systems immunology reveals a late juncture linked to fatal COVID-19
Liu C, Martins AJ, Lau WW, Rachmaninoff N, Chen J, Imberti L, Mostaghimi D, Fink DL, Burbelo PD, Dobbs K, Delmonte OM, Bansal N, Failla L, Sottini A, Quiros-Roldan E, Lee Han K, Sellers BA, Cheung F, Sparks R, Chun TW, Moir S, Lionakis MS, , Rossi C, Su H, Kuhns D, Cohen J, Notarangelo L, Tsang J, , Abers M, Apps R, Bosticardo M, Milanez-Almeida P, Mulè M, Shaw E, Zhang Y, , Castelli F, Muiesan M, Tomasoni G, Scolari F, Tucci A. Time-resolved systems immunology reveals a late juncture linked to fatal COVID-19. Cell 2021, 184: 1836-1857.e22. PMID: 33713619, PMCID: PMC7874909, DOI: 10.1016/j.cell.2021.02.018.Peer-Reviewed Original ResearchConceptsFatal COVID-19Peripheral immune cellsPlasmacytoid dendritic cellsPost-symptom onsetCOVID-19 patientsCOVID-19Fatty acid metabolismGene expression signaturesNK cellsSymptom onsetDendritic cellsSevere patientsFatal outcomeImmune response variationCellular inflammationImmune cellsInflammatory responseCell receptor sequencesExtensive patientClinical monitoringTherapeutic interventionsCell activationDay 17Disease severitySigns of exhaustionAn immune-based biomarker signature is associated with mortality in COVID-19 patients
Abers MS, Delmonte OM, Ricotta EE, Fintzi J, Fink DL, de Jesus AAA, Zarember KA, Alehashemi S, Oikonomou V, Desai JV, Canna SW, Shakoory B, Dobbs K, Imberti L, Sottini A, Quiros-Roldan E, Castelli F, Rossi C, Brugnoni D, Biondi A, Bettini LR, D’Angio’ M, Bonfanti P, Castagnoli R, Montagna D, Licari A, Marseglia GL, Gliniewicz EF, Shaw E, Kahle DE, Rastegar AT, Stack M, Myint-Hpu K, Levinson SL, DiNubile MJ, Chertow DW, Burbelo PD, Cohen JI, Calvo KR, Tsang JS, Consortium N, Su HC, Gallin JI, Kuhns DB, Goldbach-Mansky R, Lionakis MS, Notarangelo LD. An immune-based biomarker signature is associated with mortality in COVID-19 patients. JCI Insight 2021, 6: e144455. PMID: 33232303, PMCID: PMC7821609, DOI: 10.1172/jci.insight.144455.Peer-Reviewed Original ResearchMeSH KeywordsAdrenal Cortex HormonesAdultAgedAnti-Bacterial AgentsAntibodies, Monoclonal, HumanizedAntiviral AgentsAzithromycinBiomarkersCalgranulin BCase-Control StudiesChemokine CCL2Chemokine CXCL9COVID-19Enzyme InhibitorsFemaleFerritinsGene Expression ProfilingHumansHydroxychloroquineImmunologic FactorsInterferon Type IInterferon-gammaInterleukin-1 Receptor-Like 1 ProteinInterleukin-10Interleukin-15Interleukin-2Interleukin-6LactoferrinLipocalin-2MaleMatrix Metalloproteinase 9Middle AgedMultivariate AnalysisNF-kappa BPrognosisReceptors, Tumor Necrosis Factor, Type ISARS-CoV-2Severity of Illness IndexVascular Endothelial Growth Factor Receptor-1ConceptsType I IFNI IFNSevere acute respiratory syndrome coronavirus 2Whole blood transcriptional signaturesAcute respiratory syndrome coronavirus 2Respiratory syndrome coronavirus 2Immune-based biomarkersCOVID-19 patientsSyndrome coronavirus 2Eventual disease outcomeTissue-resident cellsCoronavirus disease 2019COVID-19Type II IFNInflammatory signatureIL-10Clinical outcomesMultivariable analysisIL-15Aforementioned biomarkersCell subsetsCoronavirus 2IL-1αSoluble biomarkersInflammatory response
2020
Prevalence and pathogenicity of autoantibodies in patients with idiopathic CD4 lymphopenia
Perez-Diez A, Wong C, Liu X, Mystakelis H, song J, Lu Y, Sheikh V, Bourgeois J, Lisco A, Laidlaw E, Cudrici C, Zhu C, Li Q, Freeman A, Williamson P, Anderson M, Roby G, Tsang J, Siegel R, Sereti I. Prevalence and pathogenicity of autoantibodies in patients with idiopathic CD4 lymphopenia. Journal Of Clinical Investigation 2020, 130: 5326-5337. PMID: 32634122, PMCID: PMC7524466, DOI: 10.1172/jci136254.Peer-Reviewed Original ResearchConceptsAb-dependent cell-mediated cytotoxicityComplement-dependent cytotoxicityT cellsCD4 lymphopeniaICL patientsWhole cohortIdiopathic CD4 lymphopeniaLysis of CD4Multitude of autoantibodiesCell-mediated cytotoxicityNovel therapeutic targetPathogenicity of autoantibodiesClassical complement activationClassical complement pathwayCausal infectionLow CD4Anti-CD4Opportunistic infectionsAutoimmune diseasesComplement depositionImmune deficiencyConclusionOur dataHigh prevalencePatient seraCD4
2019
Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation
Austin JW, Buckner CM, Kardava L, Wang W, Zhang X, Melson VA, Swanson RG, Martins AJ, Zhou JQ, Hoehn KB, Fisk JN, Dimopoulos Y, Chassiakos A, O'Dell S, Smelkinson MG, Seamon CA, Kwan RW, Sneller MC, Pittaluga S, Doria-Rose NA, McDermott A, Li Y, Chun TW, Kleinstein SH, Tsang JS, Petrovas C, Moir S. Overexpression of T-bet in HIV infection is associated with accumulation of B cells outside germinal centers and poor affinity maturation. Science Translational Medicine 2019, 11 PMID: 31776286, PMCID: PMC7479651, DOI: 10.1126/scitranslmed.aax0904.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntibodies, NeutralizingAntibody AffinityAntigens, CD19B-LymphocytesCytokinesFemaleGerminal CenterHIV InfectionsHumansImmunologic MemoryLymph NodesMaleMiddle AgedMutation RatePhenotypeReceptors, Antigen, B-CellT-Box Domain ProteinsT-Lymphocytes, Helper-InducerTranscriptomeYoung AdultConceptsHIV-specific B cellsT-betGC B cellsGerminal centersB cellsLymph nodesPoor affinity maturationChronic immune activationMemory B cell compartmentAntibody-mediated immunityChronic infectious diseaseOptimal antibody responseB cell compartmentChronic human infectionsB cell receptorHIV viremiaImmunologic outcomesHIV infectionViremic individualsChronic viremiaImmune activationPeripheral bloodProtective antibodiesAntibody responseCD19
2017
Assessment of Variability in the SOMAscan Assay
Candia J, Cheung F, Kotliarov Y, Fantoni G, Sellers B, Griesman T, Huang J, Stuccio S, Zingone A, Ryan B, Tsang J, Biancotto A. Assessment of Variability in the SOMAscan Assay. Scientific Reports 2017, 7: 14248. PMID: 29079756, PMCID: PMC5660188, DOI: 10.1038/s41598-017-14755-5.Peer-Reviewed Original ResearchTranscriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria
Matsuyama M, Martins A, Shallom S, Kamenyeva O, Kashyap A, Sampaio E, Kabat J, Olivier K, Zelazny A, Tsang J, Holland S. Transcriptional Response of Respiratory Epithelium to Nontuberculous Mycobacteria. American Journal Of Respiratory Cell And Molecular Biology 2017, 58: 241-252. PMID: 28915071, PMCID: PMC5806000, DOI: 10.1165/rcmb.2017-0218oc.Peer-Reviewed Original ResearchConceptsCholesterol biosynthesisUpregulation of genesRespiratory epitheliumGene expression signaturesCiliary genesTranscriptional responseRNA sequencingEpithelial cell infectionResponse genesInflammatory response genesHost responseCytokine/chemokine productionRespiratory epithelial cell culturesEpithelial cell culturesPulmonary nontuberculous mycobacteria (NTM) diseaseExpression signaturesMajor host responsesCytokines/chemokinesGenesRespiratory epithelial cellsCiliary functionNontuberculous mycobacteria diseaseCell infectionMultiplicity of infectionBiosynthesis
2016
Effects of Systemically Administered Hydrocortisone on the Human Immunome
Olnes M, Kotliarov Y, Biancotto A, Cheung F, Chen J, Shi R, Zhou H, Wang E, Tsang J, Nussenblatt R. Effects of Systemically Administered Hydrocortisone on the Human Immunome. Scientific Reports 2016, 6: 23002. PMID: 26972611, PMCID: PMC4789739, DOI: 10.1038/srep23002.Peer-Reviewed Original ResearchMeSH KeywordsAdultB-Lymphocyte SubsetsCluster AnalysisDose-Response Relationship, DrugFemaleFlow CytometryGene Expression ProfilingHumansHydrocortisoneImmunophenotypingInfusions, IntravenousKiller Cells, NaturalLymphocyte CountLymphocyte SubsetsMaleMiddle AgedSignal TransductionT-Lymphocyte SubsetsTime FactorsTranscriptomeYoung AdultConceptsSystemic corticosteroid administrationNK cell numbersHigh-dimensional flow cytometryEffect of corticosteroidsNatural killer cellsT cell subsetsEffects of systemicallyImmune system parametersAdministration of hydrocortisoneNF-κB signalingPaucity of dataHuman immunomeIntravenous hydrocortisoneCorticosteroid administrationLymphocyte subsetsNK cellsKiller cellsCell subsetsHC infusionsT cellsT lymphocytesHealthy humansGlucocorticoid receptorLow dosesCorticosteroids