2023
Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression
Jajosky R, Patel K, Allen J, Zerra P, Chonat S, Ayona D, Maier C, Morais D, Wu S, Luckey C, Eisenbarth S, Roback J, Fasano R, Josephson C, Manis J, Chai L, Hendrickson J, Hudson K, Arthur C, Stowell S. Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression. Blood 2023, 142: 1082-1098. PMID: 37363865, PMCID: PMC10541552, DOI: 10.1182/blood.2022018591.Peer-Reviewed Original ResearchConceptsAntibody-mediated immunosuppressionRBC alloantigensImmune responseFetal red blood cell antigensTarget antigenRed blood cell antigensRh immune globulinMaternal immune responseBlood cell antigensInclusion of antibodiesRBC removalAnti-RhD antibodiesAbility of antibodiesImmune globulinAntibody responseHemolytic diseaseRBC clearanceCell antigensFetal RBCsAntibody characteristicsAlloantigensSimilar interventionsAntibodiesAntigenPolyclonal antibody preparationClass switching is differentially regulated in RBC alloimmunization and vaccination
Prakash A, Medved J, Arneja A, Niebuhr C, Li A, Tarrah S, Boscia A, Burnett E, Singh A, Salazar J, Xu W, Santhanakrishnan M, Hendrickson J, Luckey C. Class switching is differentially regulated in RBC alloimmunization and vaccination. Transfusion 2023, 63: 826-838. PMID: 36907655, PMCID: PMC10851675, DOI: 10.1111/trf.17301.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsErythrocytesHumansImmunoglobulin Class SwitchingImmunoglobulin GIsoantibodiesMiceVaccinationConceptsSTAT6 KO miceSTAT6-deficient miceHOD RBCsRole of STAT6IgG subtypesRBC alloimmunizationKO miceDeficient miceTotal IgG responseIgG subclass distributionRBC transfusionIgG responsesWT miceAntibody responseIgG3 subclassSubclass distributionIgG subclassesMouse modelHuman patientsVaccinationMiceStudy designAltered levelsSubtypesClass switchingStorage differentially impacts alloimmunization to distinct red cell antigens following transfusion in mice
Maier C, Jajosky R, Patel S, Verkerke H, Fuller M, Allen J, Zerra P, Fasano R, Chonat S, Josephson C, Gibb D, Eisenbarth S, Luckey C, Hudson K, Hendrickson J, Arthur C, Stowell S. Storage differentially impacts alloimmunization to distinct red cell antigens following transfusion in mice. Transfusion 2023, 63: 457-462. PMID: 36708051, PMCID: PMC10414794, DOI: 10.1111/trf.17251.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigensErythrocyte TransfusionErythrocytesImmunoglobulin GIsoantibodiesIsoantigensMiceConceptsKEL RBCsAntibody formationAntigen levelsRed blood cell alloimmunizationIgG antibody productionDifferent clinical outcomesIgG antibody formationRed cell antigensAlloantibody productionRBC alloimmunizationClinical outcomesTransfusionAlloimmunizationRBC clearanceCell antigensClinical experienceSpecific antigenAntibody productionRBC antigensRBC survivalAntibody developmentModel antigenAntigenAdditional studiesFresh RBCsPrior immunization against an intracellular antigen enhances subsequent red blood cell alloimmunization in mice
Jajosky R, Patel S, Wu S, Patel K, Covington M, Vallecillo-Zúniga M, Ayona D, Bennett A, Luckey C, Hudson K, Hendrickson J, Eisenbarth S, Josephson C, Zerra P, Stowell S, Arthur C. Prior immunization against an intracellular antigen enhances subsequent red blood cell alloimmunization in mice. Blood 2023, 141: 2642-2653. PMID: 36638335, PMCID: PMC10356576, DOI: 10.1182/blood.2022016588.Peer-Reviewed Original ResearchConceptsCD4 T cell responsesT cell responsesIntracellular antigensB cellsImmune primingRed blood cell alloimmunizationBlood cell alloantigensRate of alloimmunizationAdditional alloantibodiesAlloimmunization rateRBC alloantigensSubsequent transfusionsSame alloantigensPrior immunizationTransfusion recipientsDonor RBCsMouse modelNumerous antigensRBC antigensAlloantigensAlloimmunizationAntigenTransfusionAlloantibodiesRBCs
2022
FcγRIV is required for IgG2c mediated enhancement of RBC alloimmunization
Qiu A, Miller A, Dei Zotti F, Santhanakrishnan M, Hendrickson JE, Tredicine M, Stowell SR, Luckey CJ, Zimring JC, Hudson KE. FcγRIV is required for IgG2c mediated enhancement of RBC alloimmunization. Frontiers In Immunology 2022, 13: 972723. PMID: 36189253, PMCID: PMC9519184, DOI: 10.3389/fimmu.2022.972723.Peer-Reviewed Original ResearchConceptsAlloantibody productionRBC alloimmunizationPassive immunizationRBC clearanceSplenic dendritic cell subsetsRed blood cell transfusionSplenic conventional DCsBlood cell transfusionDendritic cell subsetsConventional DCsFc gamma receptorsHumoral alloimmunizationAlloantibody responsesCell transfusionMaternal alloimmunizationCell subsetsFcγR expressionIgG antibodiesHemolytic diseaseBlocking antibodiesAlloimmunizationImmune complexesMouse modelKnockout miceAntibodiesClodronate inhibits alloimmunization against distinct red blood cell alloantigens in mice
Arthur CM, Patel SR, Sharma A, Zerra PE, Chonat S, Jajosky RP, Fasano RM, Patel R, Bennett A, Zhou X, Luckey CJ, Hudson KE, Eisenbarth SC, Josephson CD, Roback JD, Hendrickson JE, Stowell SR. Clodronate inhibits alloimmunization against distinct red blood cell alloantigens in mice. Transfusion 2022, 62: 948-953. PMID: 35470900, PMCID: PMC9491148, DOI: 10.1111/trf.16872.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsClodronic AcidErythrocytesHumansImmunoglobulin GImmunoglobulin MIsoantibodiesIsoantigensMiceConceptsRBC alloimmunizationRBC transfusionAntibody formationPreclinical modelsRed blood cell transfusionBlood cell alloantigensBlood cell transfusionTransfusion of RBCsTransfusion-dependent patientsDevelopment of alloantibodiesIgG antibody formationAlloantigen exposureHOD RBCsCell transfusionPost transfusionAlloantibody formationPharmacological removalIgG antibodiesTransfusionAlloimmunizationClodronateMarginal sinusPrior treatmentDay 5KEL antigenInnate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88.
Soldatenko A, Hoyt LR, Xu L, Calabro S, Lewis SM, Gallman AE, Hudson KE, Stowell SR, Luckey CJ, Zimring JC, Liu D, Santhanakrishnan M, Hendrickson JE, Eisenbarth SC. Innate and Adaptive Immunity to Transfused Allogeneic RBCs in Mice Requires MyD88. The Journal Of Immunology 2022, 208: 991-997. PMID: 35039331, PMCID: PMC10107373, DOI: 10.4049/jimmunol.2100784.Peer-Reviewed Original ResearchConceptsPattern recognition receptorsDendritic cellsDC activationAdaptive immunityClass of PRRsNon-ABO alloantibodiesRecipient dendritic cellsSplenic dendritic cellsMouse RBCsInflammatory cytokine responseTreatment of anemiaRBC transfusion therapyTransfused RBCsAlloantibody responsesAllogeneic RBCsSerious complicationsCytokine responsesTransfusion therapyRecognition receptorsMyD88TransfusionAlloimmunizationRBCsTRIFUnknown mechanism
2021
The lysophospholipid‐binding molecule CD1D is not required for the alloimmunization response to fresh or stored RBCs in mice despite RBC storage driving alterations in lysophospholipids
Medved J, Knott BM, Tarrah SN, Li AN, Shah N, Moscovich TC, Boscia AR, Salazar JE, Santhanakrishnan M, Hendrickson JE, Fu X, Zimring JC, Luckey CJ. The lysophospholipid‐binding molecule CD1D is not required for the alloimmunization response to fresh or stored RBCs in mice despite RBC storage driving alterations in lysophospholipids. Transfusion 2021, 61: 2169-2178. PMID: 34181769, PMCID: PMC8856511, DOI: 10.1111/trf.16554.Peer-Reviewed Original ResearchMeSH KeywordsAlarminsAnimalsAntibody SpecificityAntigens, CD1dBlood PreservationBlood TransfusionDuffy Blood-Group SystemErythrocytesFemaleImmunizationImmunoglobulin GImmunoglobulin MIsoantibodiesIsoantigensLysophospholipidsMaleMass SpectrometryMiceMice, Inbred StrainsMice, KnockoutMice, TransgenicMuramidaseOvalbuminReceptors, Cell SurfaceTransfusion ReactionConceptsCD1d-deficient miceCD1d deficiencyRBC alloimmunizationImmune activationNonclassical major histocompatibility complex class IWild-type control miceMajor histocompatibility complex class IHistocompatibility complex class IAdverse clinical consequencesSignificant adverse clinical consequencesLow baseline levelsRBC storageComplex class IHOD RBCsMolecule CD1dRBC transfusionWT miceControl miceImmune responseClinical consequencesMouse modelCD1dCD1d recognitionPolyclonal immunoglobulinsBaseline levelsComplement Plays a Critical Role in Inflammation-Induced Immunoprophylaxis Failure in Mice
Escamilla-Rivera V, Santhanakrishnan M, Liu J, Gibb DR, Forsmo JE, Foxman EF, Eisenbarth SC, Luckey CJ, Zimring JC, Hudson KE, Stowell SR, Hendrickson JE. Complement Plays a Critical Role in Inflammation-Induced Immunoprophylaxis Failure in Mice. Frontiers In Immunology 2021, 12: 704072. PMID: 34249009, PMCID: PMC8270673, DOI: 10.3389/fimmu.2021.704072.Peer-Reviewed Original ResearchConceptsImmunoprophylaxis failureRed blood cellsRBC transfusionComplement receptorsHuman KEL glycoproteinB cell activation thresholdWild-type micePresence of complementMurine red blood cellsTwo-hit modelRecipient inflammationIgG alloantibodiesInflammatory monocytesAdaptive immunityType miceB cellsRecipient complementTranslational relevanceKey cellsTransfusionMiceBlood cellsImmunoprophylaxis efficacyBaseline stateActivation thresholdMarginal zone B cells mediate a CD4 T-cell–dependent extrafollicular antibody response following RBC transfusion in mice
Zerra PE, Patel SR, Jajosky RP, Arthur CM, McCoy JW, Allen JWL, Chonat S, Fasano RM, Roback JD, Josephson CD, Hendrickson J, Stowell SR. Marginal zone B cells mediate a CD4 T-cell–dependent extrafollicular antibody response following RBC transfusion in mice. Blood 2021, 138: 706-721. PMID: 33876205, PMCID: PMC8394907, DOI: 10.1182/blood.2020009376.Peer-Reviewed Original ResearchConceptsMarginal zone B cellsRBC transfusionMZ B cellsB cellsHOD RBCsAlloantibody formationAntibody responseAntibody formationAntigen-specific germinal center B cellsB cell-deficient recipientsCD4 T-cell depletionRed blood cell transfusionCD4 T cell activationRBC alloantibody formationBlood cell transfusionT-cell depletionCD4 T cellsProbability of complicationsExtrafollicular antibody responsesGerminal center B cellsFollicular B cellsT cell activationRBC alloimmunizationCell transfusionSubsequent transfusions
2012
Effects of genetic, epigenetic, and environmental factors on alloimmunization to transfused antigens: Current paradigms and future considerations
Zimring J, Stowell S, Johnsen J, Hendrickson J. Effects of genetic, epigenetic, and environmental factors on alloimmunization to transfused antigens: Current paradigms and future considerations. Transfusion Clinique Et Biologique 2012, 19: 125-131. PMID: 22682308, DOI: 10.1016/j.tracli.2012.03.002.Peer-Reviewed Original ResearchConceptsImmune systemLarge observational studiesMinority of recipientsHuman immune systemTransfused cellsContext of transfusionRed blood cellsTransfusion therapyObservational studyImmune responseAdditional antibodiesCoagulation factorsAlloimmunizationClinical barriersBlood cellsRecent mechanistic studiesRecipientsTransfusionPatientsPotential causesAntigenAntibodiesMicrobial pathogensCellsResponse