2023
Platelet response to influenza vaccination reflects effects of aging
Konstorum A, Mohanty S, Zhao Y, Melillo A, Vander Wyk B, Nelson A, Tsang S, Blevins T, Belshe R, Chawla D, Rondina M, Gill T, Montgomery R, Allore H, Kleinstein S, Shaw A. Platelet response to influenza vaccination reflects effects of aging. Aging Cell 2023, 22: e13749. PMID: 36656789, PMCID: PMC9924941, DOI: 10.1111/acel.13749.Peer-Reviewed Original ResearchConceptsCommunity-dwelling older adultsPlatelet activationOlder adultsInfluenza vaccinationAge-associated chronic inflammationInfluence platelet functionRNA expressionPro-inflammatory diseasesAge-associated increasePlatelet activation pathwaysAge-associated differencesActivation pathwayPlatelet transcriptomeGeriatric conditionsChronic inflammationImmune responsePlatelet functionPlatelet responseSNF residentsVaccinationActivation responseYoung individualsProtein levelsAdultsYounger participants
2021
Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes.
Mandel-Brehm C, Fichtner ML, Jiang R, Winton VJ, Vazquez SE, Pham MC, Hoehn KB, Kelleher NL, Nowak RJ, Kleinstein SH, Wilson MR, DeRisi JL, O'Connor KC. Elevated N-Linked Glycosylation of IgG V Regions in Myasthenia Gravis Disease Subtypes. The Journal Of Immunology 2021, 207: 2005-2014. PMID: 34544801, PMCID: PMC8492536, DOI: 10.4049/jimmunol.2100225.Peer-Reviewed Original ResearchConceptsMyasthenia gravisB-cell-mediated autoimmune diseasesBCR repertoireCell-mediated autoimmune diseaseTotal BCR repertoireTotal circulating IgGSubset of patientsB cell repertoireElevated NGene segment usageMG subtypesAutoimmune disordersAutoimmune diseasesHealthy donorsCell repertoireDisease subtypesDistinct subtypesReceptor repertoireAdaptive immune receptor repertoiresV regionsAutoantigen bindingPatientsSegment usageSubtypesImmune receptor repertoiresSex-Biased Aging Effects on Ig Somatic Hypermutation Targeting
Cui A, Chawla DG, Kleinstein SH. Sex-Biased Aging Effects on Ig Somatic Hypermutation Targeting. The Journal Of Immunology 2021, 206: 101-108. PMID: 33288546, PMCID: PMC8582005, DOI: 10.4049/jimmunol.2000576.Peer-Reviewed Original ResearchConceptsOlder individualsDNA mismatch repair genesSex groupsObserved clinical differencesMismatch repair genesB cell IgDecreased expression levelDNA repair activityImmunologic responseClinical differencesAb responsesFemale human subjectsOld maleAged individualsImpaired levelDifferent agesYounger counterpartsPhase ILargest fold changeYoung individualsError-prone DNA repair activityExpression levelsHuman subjectsMutation patternsRepair activity
2020
Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis
Jiang R, Hoehn KB, Lee CS, Pham MC, Homer RJ, Detterbeck FC, Aban I, Jacobson L, Vincent A, Nowak RJ, Kaminski HJ, Kleinstein SH, O'Connor KC. Thymus-derived B cell clones persist in the circulation after thymectomy in myasthenia gravis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 30649-30660. PMID: 33199596, PMCID: PMC7720237, DOI: 10.1073/pnas.2007206117.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAutoantibodiesBiomarkersB-LymphocytesClonal EvolutionClonal Selection, Antigen-MediatedDisease SusceptibilityFemaleHumansLymphocyte CountMaleMiddle AgedModels, BiologicalMyasthenia GravisRadioimmunoassayReceptors, CholinergicThymectomyThymus GlandV(D)J RecombinationYoung AdultConceptsB cell clonesMyasthenia gravisB cell repertoireB cellsCell clonesPlasma cellsCell repertoireAdditional immunosuppressive treatmentDiminished clinical responseThymic lymphofollicular hyperplasiaComplete stable remissionMajority of patientsAntigen-experienced B cellsRandomized clinical trialsClinical symptom measuresAChR autoantibodiesImmunosuppressive treatmentSteroid doseAutoantibody titersMG thymusClinical responseStable remissionClinical scoresAutoimmune diseasesClinical trialsSeasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults
Avey S, Mohanty S, Chawla DG, Meng H, Bandaranayake T, Ueda I, Zapata HJ, Park K, Blevins TP, Tsang S, Belshe RB, Kaech SM, Shaw AC, Kleinstein SH. Seasonal Variability and Shared Molecular Signatures of Inactivated Influenza Vaccination in Young and Older Adults. The Journal Of Immunology 2020, 204: 1661-1673. PMID: 32060136, PMCID: PMC7755271, DOI: 10.4049/jimmunol.1900922.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAgingAntibodies, ViralCohort StudiesFemaleGene Expression ProfilingHemagglutination Inhibition TestsHumansImmunogenicity, VaccineInfluenza A virusInfluenza VaccinesInfluenza, HumanMaleNK Cell Lectin-Like Receptor Subfamily BOligonucleotide Array Sequence AnalysisSeasonsTranscriptomeVaccinationVaccines, InactivatedYoung AdultConceptsVaccine-induced Ab responsesOlder adultsInfluenza vaccinationDays postvaccinationInfluenza vaccineAb responsesMore effective influenza vaccinesImportant public health toolInactivated influenza vaccinationSeasonal influenza vaccineVaccine-induced immunityEffective influenza vaccinesMolecular signaturesEffects of immunosenescencePublic health toolImmune signaturesVaccination seasonVaccine responsesVaccine compositionSubset of individualsAge groupsHealth toolsSingle age groupAdultsPostvaccinationSingle cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures
Zhao Y, Amodio M, Vander Wyk B, Gerritsen B, Kumar MM, van Dijk D, Moon K, Wang X, Malawista A, Richards MM, Cahill ME, Desai A, Sivadasan J, Venkataswamy MM, Ravi V, Fikrig E, Kumar P, Kleinstein SH, Krishnaswamy S, Montgomery RR. Single cell immune profiling of dengue virus patients reveals intact immune responses to Zika virus with enrichment of innate immune signatures. PLOS Neglected Tropical Diseases 2020, 14: e0008112. PMID: 32150565, PMCID: PMC7082063, DOI: 10.1371/journal.pntd.0008112.Peer-Reviewed Original ResearchConceptsZika virusCell subsetsDengue virusConcurrent dengue infectionInnate cell responsesInnate immune signaturesVirus-infected individualsDivergent clinical outcomesMosquito-borne human pathogenIntact immune responsePre-existing infectionInnate cell typesSingle-cell immune profilingPublic health importanceCell typesImmune signaturesVirus patientsWest Nile virusAcute patientsClinical outcomesImmune profilingDengue infectionImmune statusFunctional statusImmune cells
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 responseCD19Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD−CD27− Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients
Fraussen J, Marquez S, Takata K, Beckers L, Montes Diaz G, Zografou C, Van Wijmeersch B, Villar LM, O'Connor KC, Kleinstein SH, Somers V. Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD−CD27− Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients. The Journal Of Immunology 2019, 203: 1650-1664. PMID: 31391234, PMCID: PMC6736705, DOI: 10.4049/jimmunol.1801236.Peer-Reviewed Original ResearchConceptsDN B cellsDouble-negative B cellsMultiple sclerosis patientsMS patientsNegative B cellsHealthy controlsClass-switched memoryB cellsAdaptive immune receptor repertoire sequencingSclerosis patientsRepertoire sequencingFrequency of CD95Naive B cellsUnique differentiation pathwayLow CD5Proinflammatory characteristicsImmune agingCD38 expressionHealthy individualsPatientsFlow cytometryLow mutation loadCD27Repertoire analysisMaturation state
2017
Dysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing
Vander Heiden JA, Stathopoulos P, Zhou JQ, Chen L, Gilbert TJ, Bolen CR, Barohn RJ, Dimachkie MM, Ciafaloni E, Broering TJ, Vigneault F, Nowak RJ, Kleinstein SH, O'Connor KC. Dysregulation of B Cell Repertoire Formation in Myasthenia Gravis Patients Revealed through Deep Sequencing. The Journal Of Immunology 2017, 198: 1460-1473. PMID: 28087666, PMCID: PMC5296243, DOI: 10.4049/jimmunol.1601415.Peer-Reviewed Original ResearchConceptsDeep sequencing
2015
Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing
Tsioris K, Gupta NT, Ogunniyi AO, Zimnisky RM, Qian F, Yao Y, Wang X, Stern JN, Chari R, Briggs AW, Clouser CR, Vigneault F, Church GM, Garcia MN, Murray KO, Montgomery RR, Kleinstein SH, Love JC. Neutralizing antibodies against West Nile virus identified directly from human B cells by single-cell analysis and next generation sequencing. Integrative Biology 2015, 7: 1587-1597. PMID: 26481611, PMCID: PMC4754972, DOI: 10.1039/c5ib00169b.Peer-Reviewed Original ResearchConceptsHumoral responseNext-generation sequencingB cellsWest Nile virus infectionSevere neurological illnessMemory B cellsAntibody-secreting cellsCohort of subjectsWNV-specific antibodiesHuman B cellsMosquito-borne diseaseWest Nile virusAnamnestic responseAntibody responseAvailable treatmentsClinical severityAntibody isotypesNeurological illnessVaccine studiesVirus infectionGeneration sequencingInfectious diseasesPrevious exposureTherapeutic antibodiesAntibodiesAging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination
Thakar J, Mohanty S, West AP, Joshi SR, Ueda I, Wilson J, Meng H, Blevins TP, Tsang S, Trentalange M, Siconolfi B, Park K, Gill TM, Belshe RB, Kaech SM, Shadel GS, Kleinstein SH, Shaw AC. Aging-dependent alterations in gene expression and a mitochondrial signature of responsiveness to human influenza vaccination. Aging 2015, 7: 38-51. PMID: 25596819, PMCID: PMC4356402, DOI: 10.18632/aging.100720.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedAged, 80 and overAgingCells, CulturedDNA, MitochondrialFemaleGene Expression ProfilingGene Expression RegulationGenome-Wide Association StudyHumansInfluenza VaccinesInfluenza, HumanLeukocytes, MononuclearMaleMitochondriaMitochondrial TurnoverOligonucleotide Array Sequence AnalysisOxidative PhosphorylationSeasonsTime FactorsTreatment OutcomeVaccinationYoung AdultConceptsPlasma cell signatureDay 2Influenza vaccinationDay 7Cell signatureOlder adultsInfluenza vaccine responsesAdults meeting criteriaType I interferon responseAge-associated impairmentAge-dependent alterationsI interferon responseMitochondrial biogenesisResponse signatureVaccine seasonVaccine respondersFrail subjectsInfluenza vaccineVaccine responsesVaccine responsivenessGene expression microarray analysisAbsent responseYounger respondersDay 28Meeting criteria
2014
Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults
Mohanty S, Joshi SR, Ueda I, Wilson J, Blevins TP, Siconolfi B, Meng H, Devine L, Raddassi K, Tsang S, Belshe RB, Hafler DA, Kaech SM, Kleinstein SH, Trentalange M, Allore HG, Shaw AC. Prolonged Proinflammatory Cytokine Production in Monocytes Modulated by Interleukin 10 After Influenza Vaccination in Older Adults. The Journal Of Infectious Diseases 2014, 211: 1174-1184. PMID: 25367297, PMCID: PMC4366602, DOI: 10.1093/infdis/jiu573.Peer-Reviewed Original ResearchMeSH KeywordsAdultAge FactorsAgedCytokinesDual Specificity Phosphatase 1FemaleGene Expression RegulationGPI-Linked ProteinsHumansImmunity, InnateInfluenza VaccinesInfluenza, HumanInterleukin-10Interleukin-6Lipopolysaccharide ReceptorsMaleMonocytesPhosphorylationReceptors, IgGSignal TransductionSTAT3 Transcription FactorTumor Necrosis Factor-alphaVaccinationYoung AdultConceptsOlder adultsInfluenza vaccinationInflammatory monocytesInterleukin-10Cytokine productionOlder subjectsAnti-inflammatory cytokine interleukin-10Influenza vaccine antibody responseTumor necrosis factor αImpaired vaccine responsesVaccine antibody responseIL-10 productionCytokine interleukin-10Proinflammatory cytokine productionNecrosis factor αAge-associated elevationPhosphorylated signal transducerVaccine responsesAntibody responseInterleukin-6Immune responseMonocyte populationsDay 28Intracellular stainingVaccinationSystems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection
Qian F, Goel G, Meng H, Wang X, You F, Devine L, Raddassi K, Garcia MN, Murray KO, Bolen CR, Gaujoux R, Shen-Orr SS, Hafler D, Fikrig E, Xavier R, Kleinstein SH, Montgomery RR. Systems Immunology Reveals Markers of Susceptibility to West Nile Virus Infection. MSphere 2014, 22: 6-16. PMID: 25355795, PMCID: PMC4278927, DOI: 10.1128/cvi.00508-14.Peer-Reviewed Original ResearchConceptsWest Nile virus infectionVirus infectionMyeloid dendritic cellsMarker of susceptibilityPotential therapeutic strategySeverity of infectionSevere neurological diseaseOlder patientsAcute infectionDendritic cellsCXCL10 expressionDetectable yearsImmunity-related genesStratified cohortWNV infectionTherapeutic strategiesPathogenic mechanismsAnimal studiesNeurological diseasesDisease severityVivo infectionPredictive signatureInfectionProminent alterationsPrimary cellsInfluence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis
Wu YC, James LK, Vander Heiden J, Uduman M, Durham SR, Kleinstein SH, Kipling D, Gould HJ. Influence of seasonal exposure to grass pollen on local and peripheral blood IgE repertoires in patients with allergic rhinitis. Journal Of Allergy And Clinical Immunology 2014, 134: 604-612. PMID: 25171866, PMCID: PMC4151999, DOI: 10.1016/j.jaci.2014.07.010.Peer-Reviewed Original ResearchConceptsHealthy control subjectsNasal biopsy specimensAllergic rhinitisControl subjectsImmunoglobulin heavy chain geneBiopsy specimensIgE repertoireAllergic diseasesPeripheral bloodOngoing germinal center reactionsClonal relatednessNatural pollen exposureSeasonal allergic rhinitisPollen seasonRespiratory allergic diseasesIgH sequencesAntigen-driven selectionGerminal center reactionGrass pollen seasonBlood IgEAtopic statusIgG classAntibody classPatientsPollen exposureImmune Markers Associated with Host Susceptibility to Infection with West Nile Virus
Qian F, Thakar J, Yuan X, Nolan M, Murray KO, Lee WT, Wong SJ, Meng H, Fikrig E, Kleinstein SH, Montgomery RR. Immune Markers Associated with Host Susceptibility to Infection with West Nile Virus. Viral Immunology 2014, 27: 39-47. PMID: 24605787, PMCID: PMC3949440, DOI: 10.1089/vim.2013.0074.Peer-Reviewed Original ResearchConceptsWest Nile virusSevere infectionsImmune markersIL-4IL-4 levelsSerum cytokine levelsSerum IL-4Nile virusSignificant risk factorsImmune system statusPeripheral blood cellsSevere neurological diseaseCytokine levelsAntibody levelsImmune statusRisk factorsHealthy subjectsStratified cohortWNV infectionNeurological diseasesInfectionAltered expression levelsBlood cellsAltered gene expression patternsHost susceptibility