2021
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-19
2024
A unified metric of human immune health
Sparks R, Rachmaninoff N, Lau W, Hirsch D, Bansal N, Martins A, Chen J, Liu C, Cheung F, Failla L, Biancotto A, Fantoni G, Sellers B, Chawla D, Howe K, Mostaghimi D, Farmer R, Kotliarov Y, Calvo K, Palmer C, Daub J, Foruraghi L, Kreuzburg S, Treat J, Urban A, Jones A, Romeo T, Deuitch N, Moura N, Weinstein B, Moir S, Ferrucci L, Barron K, Aksentijevich I, Kleinstein S, Townsley D, Young N, Frischmeyer-Guerrerio P, Uzel G, Pinto-Patarroyo G, Cudrici C, Hoffmann P, Stone D, Ombrello A, Freeman A, Zerbe C, Kastner D, Holland S, Tsang J. A unified metric of human immune health. Nature Medicine 2024, 30: 2461-2472. PMID: 38961223, DOI: 10.1038/s41591-024-03092-6.Peer-Reviewed Original ResearchClinically healthy individualsHealthy individualsImmune cell frequenciesImmune healthInflammatory biomarkers C-reactive proteinC-reactive proteinBiomarkers C-reactive proteinResponse to immunizationAntibody response to immunizationInflammatory disease statesImmune pathologyDisease activityTreatment responseAntigenic stimulationImmune consequencesClinical dataImmunological pathwaysHealthy controlsCell frequencyInterleukin-6Nonimmunologic diseasesImmune diseasesMonogenic diseasesMonogenic conditionsMedication use
2025
A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants
Olaloye O, Gu W, Gehlhaar A, Sabuwala B, Eke C, Li Y, Kehoe T, Farmer R, Gabernet G, Lucas C, Tsang J, Lakhani S, Taylor S, Tseng G, Kleinstein S, Konnikova L. A single-cell atlas of circulating immune cells over the first 2 months of age in extremely premature infants. Science Translational Medicine 2025, 17: eadr0942. PMID: 40043141, DOI: 10.1126/scitranslmed.adr0942.Peer-Reviewed Original ResearchConceptsExtremely premature infantsFull-term infantsT cellsMonths of lifePremature infantsImmune cellsMemory CD4<sup>+</sup> T cellsCD4<sup>+</sup> T cellsMemory-like T cellsAnalysis of immune cellsNaive CD4<sup>+</sup>Peripheral T cell developmentWeeks of gestationCord blood samplesNatural killer cellsT helper 1B cell receptor sequencesT cell developmentCycling T cellsMonths of ageSingle-cell suspensionsAmount of bloodSusceptibility to infectionCD4<sup>+</sup>Killer cells
2023
Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine
de Assis F, Hoehn K, Zhang X, Kardava L, Smith C, Merhebi O, Buckner C, Trihemasava K, Wang W, Seamon C, Chen V, Schaughency P, Cheung F, Martins A, Chiang C, Li Y, Tsang J, Chun T, Kleinstein S, Moir S. Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine. Cell Reports 2023, 42: 112780. PMID: 37440409, PMCID: PMC10529190, DOI: 10.1016/j.celrep.2023.112780.Peer-Reviewed Original ResearchConceptsMemory B cellsB cell receptorB cellsAtypical memory B cellsInfection-naïve individualsTwo-dose SARSSARS-CoV-2 mRNAB cell responsesAntibody-secreting cellsMonth 6Protective immunityCell responsesCell receptorClonal expansionImmunoglobulin GEarly timepointsLater timepointsPlasmablastsVaccinationCD71TimepointsSurface proteinsCellsMultimodal single-cell analysisMRNA
2022
Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children
Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Oguz C, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Kitakule M, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, McGuire P, Pittaluga S, Germain R, Apps R, Schwartz D, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P, Manthiram K. Adaptive immune responses to SARS-CoV-2 persist in the pharyngeal lymphoid tissue of children. Nature Immunology 2022, 24: 186-199. PMID: 36536106, PMCID: PMC10777159, DOI: 10.1038/s41590-022-01367-z.Peer-Reviewed Original ResearchConceptsT cell receptorImmune responseGerminal centersPrevious SARS-CoV-2 infectionSARS-CoV-2 infectionB-cell receptor sequencingTissue-specific immunityCell receptor sequencingAdaptive immune responsesUpper respiratory tractMemory B cellsT cell clonotypesSite of infectionSARS-CoV-2Pharyngeal lymphoid tissuePeripheral bloodLymphocyte populationsLymphoid tissueRespiratory tractCell clonotypesAdaptive immunityB cellsCDR3 sequencesAdenoidsCell receptorTranscriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses
Hagan T, Gerritsen B, Tomalin LE, Fourati S, Mulè MP, Chawla DG, Rychkov D, Henrich E, Miller HER, Diray-Arce J, Dunn P, Lee A, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Sékaly R, Kleinstein S, Pulendran B. Transcriptional atlas of the human immune response to 13 vaccines reveals a common predictor of vaccine-induced antibody responses. Nature Immunology 2022, 23: 1788-1798. PMID: 36316475, PMCID: PMC9869360, DOI: 10.1038/s41590-022-01328-6.Peer-Reviewed Original ResearchConceptsAntibody responseDay 1Vaccine-induced antibodiesYellow fever vaccineHuman immune responseMechanisms of immunityB cell activationTranscriptional atlasFever vaccineDifferent vaccinesSystems vaccinologyImmune responseMost vaccinesDay 7Cell activationInnate immunityVaccineVaccinationImmunityCommon predictorsMolecular signaturesResponsePlasmablastsInterferonAntibodiesPan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination
Fourati S, Tomalin LE, Mulè MP, Chawla DG, Gerritsen B, Rychkov D, Henrich E, Miller HER, Hagan T, Diray-Arce J, Dunn P, Levy O, Gottardo R, Sarwal M, Tsang J, Suárez-Fariñas M, Pulendran B, Kleinstein S, Sékaly R. Pan-vaccine analysis reveals innate immune endotypes predictive of antibody responses to vaccination. Nature Immunology 2022, 23: 1777-1787. PMID: 36316476, PMCID: PMC9747610, DOI: 10.1038/s41590-022-01329-5.Peer-Reviewed Original ResearchConceptsAntibody responsePro-inflammatory response genesToll-like receptor ligandsBlood transcriptional profilesHigher serum antibodyPro-inflammatory responseSerum antibodiesDifferent vaccinesImmune responseImmune stateMetabolism alterationsEndotypesImmune systemVaccinationReceptor ligandsCell proliferationGene expression characteristicsActivation stateDifferential expressionTranscriptional profilesResponse genesExpression characteristicsResponseWide variationAdjuvantThe Immune Signatures data resource, a compendium of systems vaccinology datasets
Diray-Arce J, Miller HER, Henrich E, Gerritsen B, Mulè MP, Fourati S, Gygi J, Hagan T, Tomalin L, Rychkov D, Kazmin D, Chawla DG, Meng H, Dunn P, Campbell J, Sarwal M, Tsang J, Levy O, Pulendran B, Sekaly R, Floratos A, Gottardo R, Kleinstein S, Suárez-Fariñas M. The Immune Signatures data resource, a compendium of systems vaccinology datasets. Scientific Data 2022, 9: 635. PMID: 36266291, PMCID: PMC9584267, DOI: 10.1038/s41597-022-01714-7.Peer-Reviewed Original ResearchConceptsHuman Immunology Project ConsortiumDifferent vaccinesCost-effective public health interventionsGene Expression OmnibusInfection-induced morbiditySystems immunology approachPublic health interventionsMultiple relevant studiesVaccine responsesHealth interventionsVaccineRelevant studiesVaccine discoveryUnderstanding of mechanismsMolecular signaturesImmPortSystems immunologyImmunologyStudy dataTraditional immunologyMorbidityCohortImmunogenicityMortalityReleaseRobust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children.
Manthiram K, Xu Q, Milanez-Almeida P, Martins A, Radtke A, Hoehn K, Chen J, Liu C, Tang J, Grubbs G, Stein S, Ramelli S, Kabat J, Behzadpour H, Karkanitsa M, Spathies J, Kalish H, Kardava L, Kirby M, Cheung F, Preite S, Duncker P, Romero N, Preciado D, Gitman L, Koroleva G, Smith G, Shaffer A, McBain I, Pittaluga S, Germain R, Apps R, Sadtler K, Moir S, Chertow D, Kleinstein S, Khurana S, Tsang J, Mudd P, Schwartzberg P. Robust, persistent adaptive immune responses to SARS-CoV-2 in the oropharyngeal lymphoid tissue of children. Research Square 2022 PMID: 35350206, PMCID: PMC8963700, DOI: 10.21203/rs.3.rs-1276578/v1.Peer-Reviewed Original Research
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
2016
Solving Immunology?
Vodovotz Y, Xia A, Read EL, Bassaganya-Riera J, Hafler DA, Sontag E, Wang J, Tsang JS, Day JD, Kleinstein SH, Butte AJ, Altman MC, Hammond R, Sealfon SC. Solving Immunology? Trends In Immunology 2016, 38: 116-127. PMID: 27986392, PMCID: PMC5695553, DOI: 10.1016/j.it.2016.11.006.Peer-Reviewed Original Research
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