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-19Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study
, , Rouphael N, Maecker H, Montgomery R, Diray-Arce J, Kleinstein S, Altman M, Bosinger S, Eckalbar W, Guan L, Hough C, Krammer F, Langelier C, Levy O, McEnaney K, Peters B, Rahman A, Rajan J, Sigelman S, Steen H, van Bakel H, Ward A, Wilson M, Woodruff P, Zamecnik C, Augustine A, Ozonoff A, Reed E, Becker P, Higuita N, Altman M, Atkinson M, Baden L, Becker P, Bime C, Brakenridge S, Calfee C, Cairns C, Corry D, Davis M, Augustine A, Ehrlich L, Haddad E, Erle D, Fernandez-Sesma A, Hafler D, Hough C, Kheradmand F, Kleinstein S, Kraft M, Levy O, McComsey G, Melamed E, Messer W, Metcalf J, Montgomery R, Nadeau K, Ozonoff A, Peters B, Pulendran B, Reed E, Rouphael N, Sarwal M, Schaenman J, Sekaly R, Shaw A, Simon V. Immunophenotyping assessment in a COVID-19 cohort (IMPACC): A prospective longitudinal study. Science Immunology 2021, 6: eabf3733. PMID: 34376480, PMCID: PMC8713959, DOI: 10.1126/sciimmunol.abf3733.Peer-Reviewed Original ResearchConceptsCOVID-19 cohortProspective longitudinal studyHost immune responseLongitudinal studyCOVID-19Identification of biomarkersHospitalized patientsRespiratory secretionsClinical criteriaDisease progressionImmune responseRadiographic dataImmunologic assaysEffective therapeuticsOptimal timingStudy designBiologic samplingSuch interventionsCohortSeveritySample collectionAssay protocolsPatientsSingle 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 signsCutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19
Hoehn KB, Ramanathan P, Unterman A, Sumida TS, Asashima H, Hafler DA, Kaminski N, Dela Cruz CS, Sealfon SC, Bukreyev A, Kleinstein SH. Cutting Edge: Distinct B Cell Repertoires Characterize Patients with Mild and Severe COVID-19. The Journal Of Immunology 2021, 206: 2785-2790. PMID: 34049971, PMCID: PMC8627528, DOI: 10.4049/jimmunol.2100135.Peer-Reviewed Original ResearchConceptsSevere COVID-19Mild COVID-19B cell responsesMemory B cellsB cell repertoireB cellsCell repertoireCOVID-19Cell responsesExtrafollicular B cell responsesLong-term immunitySymptomatic COVID-19Onset of symptomsB cell populationsGerminal center reactionProtective immunityPlasma cellsSingle-cell RNA sequencingCenter reactionPatientsCell populationsImmunityRNA sequencingCellsPostvaccination
2022
Single-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 interactionsPhenotypes 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 hospitalization
2023
Early cellular and molecular signatures correlate with severity of West Nile virus infection
Lee H, Zhao Y, Fleming I, Mehta S, Wang X, Vander Wyk B, Ronca S, Kang H, Chou C, Fatou B, Smolen K, Levy O, Clish C, Xavier R, Steen H, Hafler D, Love J, Shalek A, Guan L, Murray K, Kleinstein S, Montgomery R. Early cellular and molecular signatures correlate with severity of West Nile virus infection. IScience 2023, 26: 108387. PMID: 38047068, PMCID: PMC10692672, DOI: 10.1016/j.isci.2023.108387.Peer-Reviewed Original ResearchWest Nile virusEffective anti-viral responseInnate immune cell typesWest Nile virus infectionPro-inflammatory markersAcute time pointsImmune cell typesAnti-viral responseMolecular signaturesHost cellular activitiesAcute infectionAsymptomatic donorsPeripheral bloodSevere infectionsVirus infectionImmune responseSevere casesCell activityIll individualsSerum proteomicsInfectionInfection severityHigh expressionTime pointsNile virusPrior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination
Asashima H, Kim D, Wang K, Lele N, Buitrago-Pocasangre N, Lutz R, Cruz I, Raddassi K, Ruff W, Racke M, Wilson J, Givens T, Grifoni A, Weiskopf D, Sette A, Kleinstein S, Montgomery R, Shaw A, Li F, Fan R, Hafler D, Tomayko M, Longbrake E. Prior cycles of anti-CD20 antibodies affect antibody responses after repeated SARS-CoV-2 mRNA vaccination. JCI Insight 2023, 8: e168102. PMID: 37606046, PMCID: PMC10543713, DOI: 10.1172/jci.insight.168102.Peer-Reviewed Original ResearchConceptsSARS-CoV-2 mRNA vaccinationB-cell-depleted patientsB-cell depletionAntibody responseMRNA vaccinationThird doseCell depletionT cellsClaude D. Pepper Older Americans Independence CenterB cellsNational Multiple Sclerosis SocietyAnti-CD20 antibodySpike-specific antibodiesMultiple Sclerosis SocietyLow cumulative exposureLogistic regression modelsImportant clinical needCD20 therapyCD20 treatmentMost patientsThird vaccineSerologic responseVaccine dosesMRNA vaccinesVaccination strategiesMulti-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients
Diray-Arce J, Fourati S, Jayavelu N, Patel R, Maguire C, Chang A, Dandekar R, Qi J, Lee B, van Zalm P, Schroeder A, Chen E, Konstorum A, Brito A, Gygi J, Kho A, Chen J, Pawar S, Gonzalez-Reiche A, Hoch A, Milliren C, Overton J, Westendorf K, Network I, Abraham J, Adkisson M, Albert M, Torres L, Alvarenga B, Anderson M, Anderson E, Arnett A, Asashima H, Atkinson M, Baden L, Barton B, Beach K, Beagle E, Becker P, Bell M, Bernui M, Bime C, Kumar A, Booth L, Borresen B, Brakenridge S, Bristow L, Bryant R, Calfee C, Manuel J, Carrillo S, Chak S, Chang I, Connors J, Conway M, Corry D, Cowan D, Croen B, Dela Cruz C, Cusimano G, Eaker L, Edwards C, Ehrlich L, Elashoff D, Erickson H, Erle D, Farhadian S, Farrugia K, Fatou B, Fernandes A, Fernandez-Sesma A, Fragiadakis G, Furukawa S, Geltman J, Ghale R, Bermúdez M, Goonewardene M, Sanchez E, Guirgis F, Hafler D, Hamilton S, Harris P, Nemati A, Hendrickson C, Agudelo N, Hodder T, Holland S, Hough C, Huerta C, Hurley K, Hutton S, Iwasaki A, Jauregui A, Jha M, Johnson B, Joyner D, Kangelaris K, Kelly G, Khalil Z, Khan Z, Kheradmand F, Kim J, Kimura H, Ko A, Kohr B, Kraft M, Krummel M, Kutzler M, Lasky-Su J, Lee S, Lee D, Leipold M, Lentucci C, Leroux C, Lin E, Liu S, Love C, Lu Z, Maliskova L, Roth B, Manohar M, Martens M, McComsey G, McEnaney K, McLin R, Melamed E, Melnyk N, Mendez K, Messer W, Metcalf J, Michelotti G, Mick E, Mohanty S, Mosier J, Mulder L, Murphy M, Nadeau K, Nelson E, Nelson A, Nguyen V, Oberhaus J, Panganiban B, Pellegrini K, Pickering H, Powell D, Presnell S, Pulendran B, Rahman A, Sadeed A, Raskin A, Reed E, Pereira S, Rivera A, Rogers J, Rogers A, Rogowski B, Rooks R, Rosenberg-Hasson Y, Rothman J, Rousseau J, Salehi-Rad R, Saluvan M, Samaha H, Schaenman J, Schunk R, Semenza N, Sen S, Sevransky J, Seyfert-Margolis V, Shaheen T, Shaw A, Sieg S, Siegel S, Sigal N, Siles N, Simmons B, Simon V, Singh G, Sinko L, Smith C, Smolen K, Song L, Srivastava K, Sullivan P, Syphurs C, Tcheou J, Tegos G, Tharp G, Ally A, Tsitsiklis A, Ungaro R, Vaysman T, Viode A, Vita R, Wang X, Ward A, Ward D, Willmore A, Woloszczuk K, Wong K, Woodruff P, Xu L, van Haren S, van de Guchte A, Zhao Y, Cairns C, Rouphael N, Bosinger S, Kim-Schulze S, Krammer F, Rosen L, Grubaugh N, van Bakel H, Wilson M, Rajan J, Steen H, Eckalbar W, Cotsapas C, Langelier C, Levy O, Altman M, Maecker H, Montgomery R, Haddad E, Sekaly R, Esserman D, Ozonoff A, Becker P, Augustine A, Guan L, Peters B, Kleinstein S. Multi-omic longitudinal study reveals immune correlates of clinical course among hospitalized COVID-19 patients. Cell Reports Medicine 2023, 4: 101079. PMID: 37327781, PMCID: PMC10203880, DOI: 10.1016/j.xcrm.2023.101079.Peer-Reviewed Original ResearchConceptsDisease courseFatal COVID-19 diseaseHospitalized COVID-19 patientsSevere disease courseCOVID-19 participantsCOVID-19 patientsTrajectory groupsHost immune responseCOVID-19 diseaseImmune correlatesAcute infectionClinical courseHospital admissionClinical outcomesFatal outcomeClinical prognosisImmune responseSevere diseaseLongitudinal bloodNasal samplesBiologic stateLongitudinal studyDistinct assaysCohortMolecular signaturesPD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection
Asashima H, Mohanty S, Comi M, Ruff W, Hoehn K, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein S, Montgomery R, Iwasaki A, Dela Cruz C, Kaminski N, Shaw A, Hafler D, Sumida T. PD-1highCXCR5–CD4+ peripheral helper T cells promote CXCR3+ plasmablasts in human acute viral infection. Cell Reports 2023, 42: 111895. PMID: 36596303, PMCID: PMC9806868, DOI: 10.1016/j.celrep.2022.111895.Peer-Reviewed Original ResearchConceptsAcute viral infectionTph cellsViral infectionCXCR3 expressionClinical outcomesHelper TSevere viral infectionsB cell helpBetter clinical outcomesProtective humoral immunityT cell-B cell interactionsKey immune responsesPlasmablast expansionB cell differentiationCell subsetsHumoral immunityCell helpImmune responseInterferon γPlasmablast differentiationB cellsPlasmablastsCell responsesInfectionCD4
2024
IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition
Ozonoff A, Ehrlich L, Melamed E, Sesma A, Simon V, Pulendran B, Nadeau K, Davis M, McCoey G, Sekaly R, Baden L, Levy O, Schaenman J, Reed E, Shaw A, Hafler D, Montgomery R, Kleinstein S, Becker P, Augustine A, Calfee C, Erle D, DeBakey M, Corry D, Kheradmand F, Atkinson M, Brakenridge S, Higuita N, Metcalf J, Hough C, Messer W, Kraft M, Bime C, Peters B, Milliren C, Syphurs C, McEnaney K, Barton B, Lentucci C, Saluvan M, Chang A, Hoch A, Albert M, Shaheen T, Kho A, Liu S, Thomas S, Chen J, Murphy M, Cooney M, Hayati A, Bryant R, Abraham J, Jayavelu N, Presnell S, Jancsyk T, Maguire C, Qi J, Lee B, Fourati S, Esserman D, Guan L, Gygi J, Pawar S, Brito A, Fragiadakis G, Patel R, Overton J, Vita R, Westendorf K, Shannon C, Tebbutt S, Thyagarajan R, Rousseau J, Wylie D, Triplett T, Kojic E, Chinthrajah S, Ahuja N, Rogers A, Artandi M, Geng L, Yendewa G, Powell D, Kim J, Simmons B, Goonewardene I, Smith C, Martens M, Sherman A, Walsh S, Issa N, Salehi-Rad R, Dela Cruz C, Farhadian S, Iwasaki A, Ko A, Anderson E, Mehta A, Sevransky J, Seyfert-Margolis V, Leligdowicz A, Matthay M, Singer J, Kangelaris K, Hendrickson C, Krummel M, Langelier C, Woodruff P, Corry D, Kheradmand F, Anderson M, Guirgis F, Drevets D, Brown B, Siegel S, Lu Z, Mosier J, Kimura H, Khor B, van Bakel H, Rahman A, Stadlbauer D, Dutta J, Xie H, Kim-Schulze S, Gonzalez-Reiche A, van de Guchte A, Carreño J, Singh G, Raskin A, Tcheou J, Bielak D, Kawabata H, Kelly G, Patel M, Nie K, Yellin T, Fried M, Sullivan L, Morris S, Sieg S, Steen H, van Zalm P, Fatou B, Mendez K, Lasky-Su J, Hutton S, Michelotti G, Wong K, Jha M, Viode A, Kanarek N, Petrova B, Zhao Y, Bosinger S, Boddapati A, Tharp G, Pellegrini K, Beagle E, Cowan D, Hamilton S, Ribeiro S, Hodder T, Rosen L, Lee S, Wilson M, Dandekar R, Alvarenga B, Rajan J, Eckalbar W, Schroeder A, Tsitsiklis A, Mick E, Guerrero Y, Love C, Maliskova L, Adkisson M, Siles N, Geltman J, Hurley K, Saksena M, Altman D, Srivastava K, Eaker L, Bermúdez-González M, Beach K, Sominsky L, Azad A, Mulder L, Kleiner G, Lee A, Do E, Fernandes A, Manohar M, Hagan T, Blish C, Din H, Roque J, Yang S, Sigal N, Chang I, Tribout H, Harris P, Consolo M, Edwards C, Lee E, Lin E, Croen B, Semenza N, Rogowski B, Melnyk N, Bell M, Furukawa S, McLin R, Schearer P, Sheidy J, Tegos G, Nagle C, 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, Rooks R, Elashoff D, Brook J, Ramires-Sanchez E, Llamas M, Rivera A, Perdomo C, Ward D, Magyar C, Fulcher J, Pickering H, Sen S, Chaudhary O, Coppi A, Fournier J, Mohanty S, Muenker C, Nelson A, Raddassi K, Rainone M, Ruff W, Salahuddin S, Schulz W, Vijayakumar P, Wang H, Wunder E, Young H, Rothman J, Konstorum A, Chen E, Cotsapas C, Grubaugh N, Wang X, Xu L, Asashima H, Bristow L, Hussaini L, Hellmeister K, Samaha H, Wimalasena S, Cheng A, Spainhour C, Scherer E, Johnson B, Bechnak A, Ciric C, Hewitt L, Carter E, Mcnair N, Panganiban B, Huerta C, Usher J, Vaysman T, Holland S, Abe-Jones Y, Asthana S, Beagle A, Bhide S, Carrillo S, Chak S, 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, Thakur N, Vasquez J, Santhosh L, Song L, Nelson E, Moldawer L, Borresen B, Roth-Manning B, Ungaro R, Oberhaus J, Booth J, Sinko L, Brunton A, Sullivan P, Strnad M, Lyski Z, Coulter F, Micheleti C, Conway M, Francisco D, Molzahn A, Erickson H, Wilson C, Schunk R, Sierra B, Hughes T. IgM N-glycosylation correlates with COVID-19 severity and rate of complement deposition. Nature Communications 2024, 15: 404. PMID: 38195739, PMCID: PMC10776791, DOI: 10.1038/s41467-023-44211-0.Peer-Reviewed Original Research
2017
Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses
Avey S, Cheung F, Fermin D, Frelinger J, Gaujoux R, Gottardo R, Khatri P, Kleinstein S, Kotliarov Y, Meng H, Sauteraud R, Shen-Orr S, Tsang J, Vallania F, Anguiano E, Baisch J, Baldwin N, Belshe R, Blevins T, Chaussabel D, Davis M, Fikrig E, Grill D, Hafler D, Henrich E, Joshi S, Kaech S, Kennedy R, Mohanty S, Montgomery R, Oberg A, Obermoser G, Ovsyannikova I, Palucka A, Pascual V, Poland G, Pulendran B, Reinherz E, Shaw A, Siconolfi B, Stuart K, Tsang S, Ueda I, Wilson J, Zapata H. Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Science Immunology 2017, 2 PMID: 28842433, PMCID: PMC5800877, DOI: 10.1126/sciimmunol.aal4656.Peer-Reviewed Original ResearchAntibody responseInfluenza vaccination responsesVaccination responseHuman Immunology Project ConsortiumInfluenza vaccinationMulticohort analysisOlder individualsLower vaccine responsesSuccessful vaccination responseAnnual influenza vaccinationYoung individualsSubstantial antibody responseInflammatory gene signatureLarge independent studiesIndividuals 6 monthsGood antibody responsePublic health successImmune profiling studiesVaccination cohortVaccine responsesCell subsetsSmall cohortWorse responseVaccinationHealth success
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
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 cellsB cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes
Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF, Hintzen RQ, Huttner AJ, Laman JD, Nagra RM, Nylander A, Pitt D, Ramanan S, Siddiqui BA, Vigneault F, Kleinstein SH, Hafler DA, O'Connor KC. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Science Translational Medicine 2014, 6: 248ra107. PMID: 25100741, PMCID: PMC4388137, DOI: 10.1126/scitranslmed.3008879.Peer-Reviewed Original ResearchConceptsCervical lymph nodesCentral nervous systemB cellsCerebrospinal fluidLymph nodesMultiple sclerosisLymphoid tissueCNS of patientsCNS B cellsAntigen-experienced B cellsMultiple sclerosis brainSecondary lymphoid tissuesB cell compartmentB cell trafficB cell maturationImmunomodulatory therapyImmune infiltratesPeripheral bloodInflammatory diseasesLymphocyte transmigrationPeripheral tissuesNervous systemMembers of clonesCell maturationCell trafficpRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires
Vander Heiden JA, Yaari G, Uduman M, Stern JN, O'Connor KC, Hafler DA, Vigneault F, Kleinstein SH. pRESTO: a toolkit for processing high-throughput sequencing raw reads of lymphocyte receptor repertoires. Bioinformatics 2014, 30: 1930-1932. PMID: 24618469, PMCID: PMC4071206, DOI: 10.1093/bioinformatics/btu138.Peer-Reviewed Original Research
2013
Protein array–based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis
Querol L, Clark PL, Bailey MA, Cotsapas C, Cross AH, Hafler DA, Kleinstein SH, Lee JY, Yaari G, Willis SN, O'Connor KC. Protein array–based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis. Neurology 2013, 81: 956-963. PMID: 23921886, PMCID: PMC3888197, DOI: 10.1212/wnl.0b013e3182a43b48.Peer-Reviewed Original ResearchConceptsCSF of patientsMultiple sclerosisNeurologic diseaseEpstein-Barr virus infectionImmunoglobulin GElevated immunoglobulin GInflammatory neurologic diseasesSubset of patientsLarger validation cohortRecombination signal binding proteinImmunoglobulin kappa J regionCSF autoantibodiesValidation cohortControl subjectsSerum reactivityAutoantigen candidatesHigh prevalenceVirus infectionPatientsAutoantibodiesCSFSclerosisArray-based profilingDiseaseELISAModels of Somatic Hypermutation Targeting and Substitution Based on Synonymous Mutations from High-Throughput Immunoglobulin Sequencing Data
Yaari G, Vander Heiden J, Uduman M, Gadala-Maria D, Gupta N, Stern JN, O’Connor K, Hafler DA, Laserson U, Vigneault F, Kleinstein SH. Models of Somatic Hypermutation Targeting and Substitution Based on Synonymous Mutations from High-Throughput Immunoglobulin Sequencing Data. Frontiers In Immunology 2013, 4: 358. PMID: 24298272, PMCID: PMC3828525, DOI: 10.3389/fimmu.2013.00358.Peer-Reviewed Original ResearchAccurate background modelSynonymous mutationsNon-coding regionsParticular codon usageNon-functional sequencesComputational analysis methodsObserved mutation patternExisting modelsBackground modelInfluence of selectionCodon usageSHM targetingBase compositionImproved modelSequencing dataNucleotide substitutionsAnalysis methodStatistical analysisFunctional sequencesMutation targetingB-cell cancersModelSomatic hypermutation patternsMutationsHypermutation patterns