Featured Publications
Maturation of germinal center B cells after influenza virus vaccination in humans
McIntire K, Meng H, Lin T, Kim W, Moore N, Han J, McMahon M, Wang M, Malladi S, Mohammed B, Zhou J, Schmitz A, Hoehn K, Carreño J, Yellin T, Suessen T, Middleton W, Teefey S, Presti R, Krammer F, Turner J, Ward A, Wilson I, Kleinstein S, Ellebedy A. Maturation of germinal center B cells after influenza virus vaccination in humans. Journal Of Experimental Medicine 2024, 221: e20240668. PMID: 38935072, PMCID: PMC11211068, DOI: 10.1084/jem.20240668.Peer-Reviewed Original ResearchConceptsB cellsInfluenza vaccineGerminal centersAntigen-specific GC B cellsResponse to seasonal influenza vaccinationLong-lived bone marrow plasma cellsResponse to influenza vaccinationBone marrow plasma cellsGerminal center B cellsGC B cell clonesInfluenza virus vaccineMaturation of B cellsMarrow plasma cellsSeasonal influenza vaccineMemory B cellsHemagglutinin (HAB cell clonesGC B cellsInfluenza hemagglutinin (HAH5 HANeedle aspirationLymphoid structuresLymph nodesPlasma cellsGC reaction
2024
Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality
Gygi J, Maguire C, Patel R, Shinde P, Konstorum A, Shannon C, Xu L, Hoch A, Jayavelu N, Haddad E, Network I, Reed E, Kraft M, McComsey G, Metcalf J, Ozonoff A, Esserman D, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, van Bakel H, Wilson M, Eckalbar W, Maecker H, Langelier C, Steen H, Altman M, Montgomery R, Levy O, Melamed E, Pulendran B, Diray-Arce J, Smolen K, Fragiadakis G, Becker P, Sekaly R, Ehrlich L, Fourati S, Peters B, Kleinstein S, Guan L. Integrated longitudinal multiomics study identifies immune programs associated with acute COVID-19 severity and mortality. Journal Of Clinical Investigation 2024, 134: e176640. PMID: 38690733, PMCID: PMC11060740, DOI: 10.1172/jci176640.Peer-Reviewed Original ResearchConceptsClinical outcomesImmune cascadeElevated levels of inflammatory cytokinesDisease severityLevels of inflammatory cytokinesFormation of neutrophil extracellular trapsAcute COVID-19 severityCritically ill patientsNeutrophil extracellular trapsDevelopment of therapiesCOVID-19 cohortCOVID-19 severityViral clearanceImmunosuppressive metabolitesDeep immunophenotypingMultiomic modelIFN-stimulated genesImmunophenotypic assessmentB cellsDisease courseEarly upregulationInflammatory cytokinesDisease progressionIFN inhibitorsExtracellular traps
2022
Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study
Ozonoff A, Schaenman J, Jayavelu ND, Milliren CE, Calfee CS, Cairns CB, Kraft M, Baden LR, Shaw AC, Krammer F, van Bakel H, Esserman DA, Liu S, Sesma AF, Simon V, Hafler DA, Montgomery RR, Kleinstein SH, Levy O, Bime C, Haddad EK, Erle DJ, Pulendran B, Nadeau KC, Davis MM, Hough CL, Messer WB, Higuita NIA, Metcalf JP, Atkinson MA, Brakenridge SC, Corry D, Kheradmand F, Ehrlich LIR, Melamed E, McComsey GA, Sekaly R, Diray-Arce J, Peters B, Augustine AD, Reed EF, Altman MC, Becker PM, Rouphael N, Ozonoff A, Schaenman J, Jayavelu N, Milliren C, Calfee C, Cairns C, Kraft M, Baden L, Shaw A, Krammer F, van Bakel H, Esserman D, Liu S, Sesma A, Simon V, Hafler D, Montgomery R, Kleinstein S, Levy O, Bime C, Haddad E, Erle D, Pulendran B, Nadeau K, Davis M, Hough C, Messer W, Higuita N, Metcalf J, Atkinson M, Brakenridge S, Corry D, Kheradmand F, Ehrlich L, Melamed E, McComsey G, Sekaly R, Diray-Arce J, Peters B, Augustine A, Reed E, McEnaney K, Barton B, Lentucci C, Saluvan M, Chang A, Hoch A, Albert M, Shaheen T, Kho A, Thomas S, Chen J, Murphy M, Cooney M, Presnell S, Fragiadakis G, Patel R, Guan L, Gygi J, Pawar S, Brito A, Khalil Z, Maguire C, Fourati S, Overton J, Vita R, Westendorf K, Salehi-Rad R, Leligdowicz A, Matthay M, Singer J, Kangelaris K, Hendrickson C, Krummel M, Langelier C, Woodruff P, Powell D, Kim J, Simmons B, Goonewardene I, Smith C, Martens M, Mosier J, Kimura H, Sherman A, Walsh S, Issa N, Dela Cruz C, Farhadian S, Iwasaki A, Ko A, Chinthrajah S, Ahuja N, Rogers A, Artandi M, Siegel S, Lu Z, Drevets D, Brown B, Anderson M, Guirgis F, Thyagarajan R, Rousseau J, Wylie D, Busch J, Gandhi S, Triplett T, Yendewa G, Giddings O, Anderson E, Mehta A, Sevransky J, Khor B, Rahman A, Stadlbauer D, Dutta J, Xie H, Kim-Schulze S, Gonzalez-Reiche A, van de Guchte A, Farrugia K, Khan Z, Maecker H, Elashoff D, Brook J, Ramires-Sanchez E, Llamas M, Rivera A, Perdomo C, Ward D, Magyar C, Fulcher J, Abe-Jones Y, Asthana S, Beagle A, Bhide S, Carrillo S, Chak S, Fragiadakis G, Ghale R, Gonzalez A, Jauregui A, Jones N, Lea T, Lee D, Lota R, Milush J, Nguyen V, Pierce L, Prasad P, Rao A, Samad B, Shaw C, Sigman A, Sinha P, Ward A, Willmore A, Zhan J, Rashid S, Rodriguez N, Tang K, Altamirano L, Betancourt L, Curiel C, Sutter N, Paz M, Tietje-Ulrich G, Leroux C, Connors J, Bernui M, Kutzler M, Edwards C, Lee E, Lin E, Croen B, Semenza N, Rogowski B, Melnyk N, Woloszczuk K, Cusimano G, Bell M, Furukawa S, McLin R, Marrero P, Sheidy J, Tegos G, Nagle C, Mege N, Ulring K, Seyfert-Margolis V, Conway M, Francisco D, Molzahn A, Erickson H, Wilson C, Schunk R, Sierra B, Hughes T, Smolen K, Desjardins M, van Haren S, Mitre X, Cauley J, Li X, Tong A, Evans B, Montesano C, Licona J, Krauss J, Chang J, Izaguirre N, Chaudhary O, Coppi A, Fournier J, Mohanty S, Muenker M, Nelson A, Raddassi K, Rainone M, Ruff W, Salahuddin S, Schulz W, Vijayakumar P, Wang H, Wunder E, Young H, Zhao Y, Saksena M, Altman D, Kojic E, Srivastava K, Eaker L, Bermúdez-González M, Beach K, Sominsky L, Azad A, Carreño J, Singh G, Raskin A, Tcheou J, Bielak D, Kawabata H, Mulder L, Kleiner G, Lee A, Do Do E, Fernandes A, Manohar M, Hagan T, Blish C, Din H, Roque J, Yang S, Brunton A, Sullivan P, Strnad M, Lyski Z, Coulter F, Booth J, Sinko L, Moldawer L, Borresen B, Roth-Manning B, Song L, Nelson E, Lewis-Smith M, Smith J, Tipan P, Siles N, Bazzi S, Geltman J, Hurley K, Gabriele G, Sieg S, Vaysman T, Bristow L, Hussaini L, Hellmeister K, Samaha H, Cheng A, Spainhour C, Scherer E, Johnson B, Bechnak A, Ciric C, Hewitt L, Carter E, Mcnair N, Panganiban B, Huerta C, Usher J, Ribeiro S, Altman M, Becker P, Rouphael N. Phenotypes of disease severity in a cohort of hospitalized COVID-19 patients: Results from the IMPACC study. EBioMedicine 2022, 83: 104208. PMID: 35952496, PMCID: PMC9359694, DOI: 10.1016/j.ebiom.2022.104208.Peer-Reviewed Original ResearchConceptsRisk factorsRadiographic findingsFemale sexDisease severityHospitalized COVID-19 patientsSARS-CoV-2 antibodiesSARS-CoV-2 PCRLong COVID-19Presence of infiltratesInvasive mechanical ventilationCharacteristics of patientsOnly female sexViral load levelsClinical laboratory valuesCOVID-19 cohortMultivariable logistic regressionCOVID-19 patientsCoronavirus disease 2019PCR cycle thresholdCOVID-19Baseline creatinineBaseline lymphopeniaMedian ageOverall mortalityProlonged hospitalizationSingle-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19
Unterman A, Sumida TS, Nouri N, Yan X, Zhao AY, Gasque V, Schupp JC, Asashima H, Liu Y, Cosme C, Deng W, Chen M, Raredon MSB, Hoehn KB, Wang G, Wang Z, DeIuliis G, Ravindra NG, Li N, Castaldi C, Wong P, Fournier J, Bermejo S, Sharma L, Casanovas-Massana A, Vogels CBF, Wyllie AL, Grubaugh ND, Melillo A, Meng H, Stein Y, Minasyan M, Mohanty S, Ruff WE, Cohen I, Raddassi K, Niklason L, Ko A, Montgomery R, Farhadian S, Iwasaki A, Shaw A, van Dijk D, Zhao H, Kleinstein S, Hafler D, Kaminski N, Dela Cruz C. Single-cell multi-omics reveals dyssynchrony of the innate and adaptive immune system in progressive COVID-19. Nature Communications 2022, 13: 440. PMID: 35064122, PMCID: PMC8782894, DOI: 10.1038/s41467-021-27716-4.Peer-Reviewed Original ResearchMeSH KeywordsAdaptive ImmunityAgedAntibodies, Monoclonal, HumanizedCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCells, CulturedCOVID-19COVID-19 Drug TreatmentFemaleGene Expression ProfilingGene Expression RegulationHumansImmunity, InnateMaleReceptors, Antigen, B-CellReceptors, Antigen, T-CellRNA-SeqSARS-CoV-2Single-Cell AnalysisConceptsProgressive COVID-19B cell clonesSingle-cell analysisT cellsImmune responseMulti-omics single-cell analysisCOVID-19Cell clonesAdaptive immune interactionsSevere COVID-19Dynamic immune responsesGene expressionSARS-CoV-2 virusAdaptive immune systemSomatic hypermutation frequenciesCellular effectsProtein markersEffector CD8Immune signaturesProgressive diseaseHypermutation frequencyProgressive courseClassical monocytesClonesImmune interactions
2021
Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA
Oh JE, Song E, Moriyama M, Wong P, Zhang S, Jiang R, Strohmeier S, Kleinstein SH, Krammer F, Iwasaki A. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA. Science Immunology 2021, 6: eabj5129. PMID: 34890255, PMCID: PMC8762609, DOI: 10.1126/sciimmunol.abj5129.Peer-Reviewed Original ResearchConceptsVirus infectionIgA secretionB cellsMucosal surfacesIgA-secreting B cellsIgA-expressing cellsRole of IgARespiratory virus infectionsIgA-secreting cellsLower respiratory tractInfluenza virus infectionEffective immune protectionHeterologous virus infectionMemory B cellsSecretory immunoglobulin AProtein-based vaccinesB cell populationsPredominant Ig isotypeSite of entryIntranasal primingBronchoalveolar spaceProtective immunityVaccine strategiesRespiratory mucosaImmune protectionElevated 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 repertoiresSingle cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells
Jiang R, Meng H, Raddassi K, Fleming I, Hoehn KB, Dardick KR, Belperron AA, Montgomery RR, Shalek AK, Hafler DA, Kleinstein SH, Bockenstedt LK. Single cell immunophenotyping of the skin lesion erythema migrans Identifies IgM memory B cells. JCI Insight 2021, 6: e148035. PMID: 34061047, PMCID: PMC8262471, DOI: 10.1172/jci.insight.148035.Peer-Reviewed Original ResearchConceptsMemory B cellsErythema migransB cellsEM lesionsIgM memory B cellsLyme diseaseB-cell receptor sequencingSkin infection siteCell receptor sequencingEarly Lyme diseaseLocal antigen presentationSkin immune responsesB cell populationsSingle-cell immunophenotypingMHC class II genesUninvolved skinImmune cellsSpirochetal infectionAntigen presentationCell immunophenotypingT cellsImmune responseIsotype usageAntibody productionInitial signsSex-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 trialsHuman germinal centres engage memory and naive B cells after influenza vaccination
Turner JS, Zhou JQ, Han J, Schmitz AJ, Rizk AA, Alsoussi WB, Lei T, Amor M, McIntire KM, Meade P, Strohmeier S, Brent RI, Richey ST, Haile A, Yang YR, Klebert MK, Suessen T, Teefey S, Presti RM, Krammer F, Kleinstein SH, Ward AB, Ellebedy AH. Human germinal centres engage memory and naive B cells after influenza vaccination. Nature 2020, 586: 127-132. PMID: 32866963, PMCID: PMC7566073, DOI: 10.1038/s41586-020-2711-0.Peer-Reviewed Original ResearchConceptsB cell clonesInfluenza vaccinationGerminal center B cellsB cellsGerminal center reactionCell clonesLymph nodesMonoclonal antibodiesPre-existing memory B cellsGerminal center B cell responsesStrain-specific monoclonal antibodiesCenter reactionUltrasound-guided fine-needle aspirationMajor public health threatEarly plasmablast responsesInfluenza virus vaccinationSeasonal influenza vaccinationCross-reactive monoclonal antibodiesB cell responsesMemory B cellsB-cell originFine-needle aspirationNaive B cellsPublic health threatHuman germinal centreSeasonal 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 stateEarly B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production
Cotzomi E, Stathopoulos P, Lee CS, Ritchie AM, Soltys JN, Delmotte FR, Oe T, Sng J, Jiang R, K A, Vander Heiden JA, Kleinstein SH, Levy M, Bennett JL, Meffre E, O’Connor K. Early B cell tolerance defects in neuromyelitis optica favour anti-AQP4 autoantibody production. Brain 2019, 142: 1598-1615. PMID: 31056665, PMCID: PMC6536857, DOI: 10.1093/brain/awz106.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderB cell tolerance checkpointsNMOSD patientsNaïve B cellsAQP4 autoantibodiesTolerance checkpointsHealthy donorsB cellsEarly B cell tolerance checkpointsPeripheral B cell tolerance checkpointsMature naïve B cellsB cell tolerance defectsSeropositive NMOSD patientsOptica spectrum disorderRare autoimmune disorderNaïve B-cell compartmentB cell compartmentB cell populationsAquaporin-4 water channelsPathogenic autoantibodiesAutoantibody productionOptic nerveAutoimmune disordersSevere inflammationSpinal cord
2018
Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers
Rydyznski CE, Cranert SA, Zhou JQ, Xu H, Kleinstein SH, Singh H, Waggoner SN. Affinity Maturation Is Impaired by Natural Killer Cell Suppression of Germinal Centers. Cell Reports 2018, 24: 3367-3373.e4. PMID: 30257198, PMCID: PMC6192537, DOI: 10.1016/j.celrep.2018.08.075.Peer-Reviewed Original ResearchConceptsNK cellsGC B cell frequencyNatural killer cell suppressionAntigen-reactive B cellsB cell frequenciesNatural killer cellsFollicular helper TAntigen-specific immunoglobulinsAdministration of alumGerminal center reactionVaccine elicitationHelper TKiller cellsHumoral immunityProtective antibodiesHigh-affinity antibodiesCell suppressionGerminal centersB cellsCell frequencyCenter reactionSomatic hypermutationGC developmentGC reactionAntibody affinity
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
2016
Age‐associated vascular inflammation promotes monocytosis during atherogenesis
Du W, Wong C, Song Y, Shen H, Mori D, Rotllan N, Price N, Dobrian AD, Meng H, Kleinstein SH, Fernandez‐Hernando C, Goldstein DR. Age‐associated vascular inflammation promotes monocytosis during atherogenesis. Aging Cell 2016, 15: 766-777. PMID: 27135421, PMCID: PMC4933655, DOI: 10.1111/acel.12488.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsAortaAtherosclerosisBlood VesselsCell CountChemotaxisCulture Media, ConditionedDiet, High-FatDown-RegulationHematopoiesisHemodynamicsInflammationInflammation MediatorsInsulin ResistanceInterleukin-6LeukocytosisMacrophagesMaleMiceMice, Inbred C57BLMonocytesOligonucleotide Array Sequence AnalysisReceptors, LDLStromal CellsUp-RegulationConceptsHigh-fat dietVascular inflammationMacrophage accumulationAtherosclerotic aortaBone marrow transplant experimentsStromal factorsElevated blood pressureVascular smooth muscle cellsLow-fat dietSmooth muscle cellsBlood pressurePeripheral monocytosisProinflammatory stateInflammatory stateLDL levelsIL-6Insulin resistancePeripheral bloodEnhanced atherogenesisInflammatory responseMetabolic dysfunctionYoung aortasMurine modelProduction of osteopontinCCL-2Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production
Cao Y, Amezquita RA, Kleinstein SH, Stathopoulos P, Nowak RJ, O'Connor KC. Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production. The Journal Of Immunology 2016, 196: 2075-2084. PMID: 26826242, PMCID: PMC4761502, DOI: 10.4049/jimmunol.1501339.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAutoimmunityCD4-Positive T-LymphocytesCell SeparationCytokinesEnzyme-Linked Immunosorbent AssayFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansInterferon-gammaInterleukin-10Interleukin-17MaleMiddle AgedMyasthenia GravisPhenotypePolymerase Chain ReactionT-Lymphocyte SubsetsConceptsAutoreactive T cellsT cell compartmentHealthy control subjectsMyasthenia gravisT cellsMG patientsIL-17Control subjectsT cell librariesB cellsGM-CSFMemory T cell compartmentElevated IL-17Prototypical autoimmune diseaseIL-10 productionMemory T cellsCell compartmentIL-10 expressionB cell compartmentPathogenic phenotypeMG cohortPathogenic autoantibodiesAutoimmune responseClinical manifestationsProinflammatory phenotype
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 antibodiesAntibodies