2020
Fc Gamma Receptors and Complement Component 3 Facilitate Anti-fVIII Antibody Formation
Zerra PE, Arthur CM, Chonat S, Maier CL, Mener A, Shin S, Allen JWL, Baldwin WH, Cox C, Verkerke H, Jajosky RP, Tormey CA, Meeks SL, Stowell SR. Fc Gamma Receptors and Complement Component 3 Facilitate Anti-fVIII Antibody Formation. Frontiers In Immunology 2020, 11: 905. PMID: 32582142, PMCID: PMC7295897, DOI: 10.3389/fimmu.2020.00905.Peer-Reviewed Original ResearchConceptsAnti-FVIII antibody formationAnti-FVIII antibodiesKnockout recipientsAntibody formationWT recipientsFc gamma receptorsAnti-FVIII antibody developmentGamma receptorsRole of FcγRsFVIII exposureAntibody levelsWT miceTherapeutic optionsAntibody responseC3 knockoutTarget antigenHemophilia AImmune systemFcγRAntibody developmentInfusionRecipientsAntibodiesPotential mechanismsPatients
2018
Marginal Zone B Cells Induce Alloantibody Formation Following RBC Transfusion
Patel SR, Gibb DR, Girard-Pierce K, Zhou X, Rodrigues LC, Arthur CM, Bennett AL, Jajosky RP, Fuller M, Maier CL, Zerra PE, Chonat S, Smith NH, Tormey CA, Hendrickson JE, Stowell SR. Marginal Zone B Cells Induce Alloantibody Formation Following RBC Transfusion. Frontiers In Immunology 2018, 9: 2516. PMID: 30505302, PMCID: PMC6250814, DOI: 10.3389/fimmu.2018.02516.Peer-Reviewed Original ResearchConceptsMZ B cellsMarginal zone B cellsRBC transfusionB cellsKEL RBCsImmune factorsAntibody formationRBC antigensRed blood cell alloimmunizationKey immune factorsSpecific immune compartmentCD4 T cellsFollicular B cellsAlloantibody formationImmune compartmentAntibody responseT cellsTherapeutic modalitiesTransfusionImmunological challengeImmune pathwaysMarginal sinusSplenic compartmentsImmune constituentsAlloimmunizationTransfused platelets enhance alloimmune responses to transfused KEL-expressing red blood cells in a murine model.
Madrid DJ, Santhanakrishnan M, Liu J, Gibb DR, Liu D, Natarajan P, Beitler D, Shi Z, Mo C, Tormey CA, Patel SR, Stowell SR, Hendrickson JE. Transfused platelets enhance alloimmune responses to transfused KEL-expressing red blood cells in a murine model. Blood Transfusion = Trasfusione Del Sangue 2018, 17: 368-377. PMID: 30418129, PMCID: PMC6774925, DOI: 10.2450/2018.0178-18.Peer-Reviewed Original ResearchConceptsRed blood cell transfusionBlood cell transfusionTransfusion of plateletsAlloimmune responseRed blood cellsCell transfusionWild-type recipientsBlood cellsImmune responseMurine modelRed blood cell alloimmunisationCD40/CD40L interactionHuman KEL glycoproteinWild-type C57BL/6Humoral immune responseAdaptive immune responsesDevelopment of alloantibodiesPlatelet-rich plasmaEndogenous plateletsCD40L interactionRecipient treatmentTransfusionDanger signalsCD40LTransgenic donors
2017
B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice
Gibb DR, Liu J, Santhanakrishnan M, Natarajan P, Madrid DJ, Patel S, Eisenbarth SC, Tormey CA, Stowell SR, Iwasaki A, Hendrickson JE. B cells require Type 1 interferon to produce alloantibodies to transfused KEL‐expressing red blood cells in mice. Transfusion 2017, 57: 2595-2608. PMID: 28836263, PMCID: PMC5745367, DOI: 10.1111/trf.14288.Peer-Reviewed Original ResearchConceptsBone marrow chimeric miceHuman KEL glycoproteinType 1 interferonB cellsMean fluorescence intensityChimeric miceRed blood cell antigensBlood cell antigensGerminal center B cellsWT B cellsRBC alloimmunizationIgG alloantibodiesAlloimmune responseB cell differentiationRed blood cellsTransfusion protocolControl miceInflammatory stateWT miceAutoimmune pathologyIgG productionIFNAR1 expressionPlasma cellsAntiviral immunityInflammatory stimuliThe impact of vaccination on RBC alloimmunization in a murine model
Natarajan P, Santhanakrishnan M, Tormey CA, Hendrickson JE. The impact of vaccination on RBC alloimmunization in a murine model. Vox Sanguinis 2017, 112: 598-600. PMID: 28597520, PMCID: PMC5575953, DOI: 10.1111/vox.12541.Peer-Reviewed Original ResearchConceptsImmune responseMurine modelRBC alloantibody formationDamage-associated molecular patternsImpact of vaccinationRBC alloimmunizationAlloantibody formationHepB vaccineRBC transfusionAdaptive immunityAnimal modelsAlloimmunizationMolecular patternsVaccineVaccinationFuture studiesResponseTransfusionImmunity
2016
Understanding red blood cell alloimmunization triggers
Hendrickson JE, Tormey CA. Understanding red blood cell alloimmunization triggers. Hematology 2016, 2016: 446-451. PMID: 27913514, PMCID: PMC6142457, DOI: 10.1182/asheducation-2016.1.446.Peer-Reviewed Original ResearchConceptsRBC alloimmunizationRed blood cellsRisk factorsBlood cellsWhite blood cellsBlood group antigensPregnancy outcomesAlloantibody formationRBC alloantibodiesRBC transfusionRecipient factorsTransfusion safetyAlloimmunizationAnimal modelsHuman studiesPrevention strategiesDonor plasmaDanger signalsParticular antigenGroup antigensAntigenTransfusionPregnancyNonrespondersCellsRed blood cell alloimmunization
Hendrickson JE, Eisenbarth SC, Tormey CA. Red blood cell alloimmunization. Current Opinion In Hematology 2016, 23: 543-549. PMID: 27454234, DOI: 10.1097/moh.0000000000000277.Peer-Reviewed Original ResearchConceptsAlloimmune responseChronic red blood cell transfusionsRed blood cell transfusionRed blood cell alloimmunizationHuman leukocyte antigen (HLA) expressionBlood cell transfusionT-cell markersRecent animal studiesResult of pregnancyRecipient inflammationSuch alloimmunizationCell transfusionDendritic cellsClinical studiesAntigen expressionImmune responseAlloimmunizationAnimal modelsAnimal studiesRBC antigensBlood groupHigher likelihoodTransfusionAdditional associationsHigh rateAntigen modulation as a potential mechanism of anti-KEL immunoprophylaxis in mice
Liu J, Santhanakrishnan M, Natarajan P, Gibb DR, Eisenbarth SC, Tormey CA, Siddon AJ, Stowell SR, Branch DR, Hendrickson JE. Antigen modulation as a potential mechanism of anti-KEL immunoprophylaxis in mice. Blood 2016, 128: 3159-3168. PMID: 27688803, PMCID: PMC5201095, DOI: 10.1182/blood-2016-06-724732.Peer-Reviewed Original ResearchConceptsMechanism of actionKO miceRed blood cell alloimmunizationGlycoprotein antigenMurine RBCsHuman KEL glycoproteinRh immune globulinSingle knockout miceWild-type recipientsImmunoprophylaxis programKO recipientsPrevent alloimmunizationImmune globulinSerious complicationsAntigen modulationMurine modelImmunoprophylaxisFcγ receptorsKEL antigenAlloimmunizationFlow cytometryRapid clearanceWestern blotMiceAntigenThe Nlrp3 Inflammasome Does Not Regulate Alloimmunization to Transfused Red Blood Cells in Mice
Gibb DR, Calabro S, Liu D, Tormey CA, Spitalnik SL, Zimring JC, Hendrickson JE, Hod EA, Eisenbarth SC. The Nlrp3 Inflammasome Does Not Regulate Alloimmunization to Transfused Red Blood Cells in Mice. EBioMedicine 2016, 9: 77-86. PMID: 27345021, PMCID: PMC4972549, DOI: 10.1016/j.ebiom.2016.06.008.Peer-Reviewed Original ResearchConceptsRBC transfusionNLRP3 inflammasomeRed blood cell transfusionInnate immune cell activationPro-inflammatory pathogensMolecular patternsBlood cell transfusionProduction of alloantibodiesTransfusion-associated mortalityImmune cell activationInnate immune stimuliBlood group antigensBone marrow failureAlloantibody productionRBC alloimmunizationAlloantibody responsesCell transfusionAlloimmune responseRed blood cellsABO matchingImmunological factorsInflammatory conditionsLeading causeImmune stimuliEndogenous DAMPBridging channel dendritic cells induce immunity to transfused red blood cells
Calabro S, Gallman A, Gowthaman U, Liu D, Chen P, Liu J, Krishnaswamy JK, Nascimento MS, Xu L, Patel SR, Williams A, Tormey CA, Hod EA, Spitalnik SL, Zimring JC, Hendrickson JE, Stowell SR, Eisenbarth SC. Bridging channel dendritic cells induce immunity to transfused red blood cells. Journal Of Experimental Medicine 2016, 213: 887-896. PMID: 27185856, PMCID: PMC4886363, DOI: 10.1084/jem.20151720.Peer-Reviewed Original ResearchConceptsSplenic dendritic cellsDendritic cellsRBC transfusionT cellsImmune responseRed blood cell transfusionBlood cell transfusionT cell primingConventional dendritic cellsDetrimental immune responsesB cell responsesNaive T cellsT cell helpMurine transfusion modelRBC transfusion supportTime of transfusionRBC alloantigensCell transfusionDC subsetsAllogeneic RBCsRed blood cellsRenal failureTransfusion supportMajor complicationsCell primingClinically significant anti‐KEL RBC alloantibodies are transferred by breast milk in a murine model
Santhanakrishnan M, Tormey CA, Natarajan P, Liu J, Hendrickson JE. Clinically significant anti‐KEL RBC alloantibodies are transferred by breast milk in a murine model. Vox Sanguinis 2016, 111: 79-87. PMID: 26950259, PMCID: PMC4938760, DOI: 10.1111/vox.12387.Peer-Reviewed Original ResearchConceptsBreast milkRBC alloantibodiesIgA antibodiesMurine modelHuman KEL glycoproteinSeries of pregnanciesBreast milk transferHuman breast milkWild-type pupsKEL RBCsNursing infantsClinical significanceAlloantibodiesNursing pupsMurine dataTransfusion experimentsMilk transferInfantsPupsTransfusionHuman dataSequelaePregnancyAnemiaPremature clearanceCD8+ T cells mediate antibody-independent platelet clearance in mice
Arthur CM, Patel SR, Sullivan HC, Winkler AM, Tormey CA, Hendrickson JE, Stowell SR. CD8+ T cells mediate antibody-independent platelet clearance in mice. Blood 2016, 127: 1823-1827. PMID: 26787734, PMCID: PMC4825415, DOI: 10.1182/blood-2015-10-673426.Peer-Reviewed Original ResearchConceptsPlatelet clearancePlatelet removalImportant therapeutic interventionPlatelet transfusionsNonimmune mechanismsT cellsTherapeutic outcomesAlloantibodiesTherapeutic interventionsAppropriate managementTransfusionClearanceSole mediatorPatientsVariety of mechanismsComplete absenceNumerous studiesCD8Clear mechanismCellsAbsenceMiceIndividualsPrevention
2015
Riboflavin‐ultraviolet light pathogen reduction treatment does not impact the immunogenicity of murine red blood cells
Tormey CA, Santhanakrishnan M, Smith NH, Liu J, Marschner S, Goodrich RP, Hendrickson JE. Riboflavin‐ultraviolet light pathogen reduction treatment does not impact the immunogenicity of murine red blood cells. Transfusion 2015, 56: 863-872. PMID: 26643781, DOI: 10.1111/trf.13432.Peer-Reviewed Original ResearchConceptsWhite blood cellsFresh whole bloodPathogen reduction treatmentAlloimmune responseWhole bloodRBC antigensSyngeneic RBCsNegative direct antiglobulin testBlood cellsRBC antigen expressionRecipient alloimmune responsesDirect antiglobulin testMurine red blood cellsPathogen inactivation treatmentPosttransfusion RBC recoveryKEL RBCsRBC alloimmunizationImmunogenic neoantigensRed blood cellsAntiglobulin testBlood donorsImmune responseAntigen expressionHours posttransfusionHuman antigensThe strengths and limitations of animal models in assessing the effects of red blood cell storage age on clinical outcomes
Gehrie EA, Tormey CA. The strengths and limitations of animal models in assessing the effects of red blood cell storage age on clinical outcomes. Transfusion 2015, 55: 2537-2540. PMID: 26559396, DOI: 10.1111/trf.13289.Peer-Reviewed Original ResearchAnti-KEL sera prevents alloimmunization to transfused KEL RBCs in a murine model
Stowell SR, Arthur CM, Girard-Pierce KR, Sullivan HC, Santhanakrishnan M, Natarajan P, Patel SR, Tormey CA, Zimring JC, Hendrickson JE. Anti-KEL sera prevents alloimmunization to transfused KEL RBCs in a murine model. Haematologica 2015, 100: e394-e397. PMID: 26185172, PMCID: PMC4591773, DOI: 10.3324/haematol.2015.128603.Peer-Reviewed Original Research
2014
Molecular immunohaematology round table discussions at the AABB Annual Meeting, Denver 2013.
Flegel WA, Castilho L, Delaney M, Klapper EB, Moulds JM, Noizat-Pirenne F, Shehata N, Stack G, Tormey CA, Wagner FF, Waxman DA, Weinstock C, Wendel S, Denomme GA. Molecular immunohaematology round table discussions at the AABB Annual Meeting, Denver 2013. Blood Transfusion = Trasfusione Del Sangue 2014, 13: 514-20. PMID: 25545874, PMCID: PMC4614304, DOI: 10.2450/2014.0213-14.Peer-Reviewed Original ResearchRed Blood Cell Alloimmunization Mitigation Strategies
Hendrickson JE, Tormey CA, Shaz BH. Red Blood Cell Alloimmunization Mitigation Strategies. Transfusion Medicine Reviews 2014, 28: 137-144. PMID: 24928468, DOI: 10.1016/j.tmrv.2014.04.008.Peer-Reviewed Original ResearchConceptsHemolytic transfusion reactionsRBC alloantibodiesRBC alloimmunizationTransfusion reactionsImmune systemRed blood cell alloantibodiesCompatible RBC unitsRBC alloimmunization rateTransfusion-associated morbidityRecipient's immune systemTransfusion-associated deathForms of anemiaAlloimmunization rateAntigen exposureSignificant morbidityTransfusion recipientsHemolytic diseaseAlloantibodiesHuman studiesAnimal studiesDanger signalsAnimal dataMorbidityAlloimmunizationRBC units
2013
Pathology Consultation on Monitoring Direct Thrombin Inhibitors and Overcoming Their Effects in Bleeding Patients
Winkler AM, Tormey CA. Pathology Consultation on Monitoring Direct Thrombin Inhibitors and Overcoming Their Effects in Bleeding Patients. American Journal Of Clinical Pathology 2013, 140: 610-622. PMID: 24124139, DOI: 10.1309/ajcp9vjs6kuknchw.Peer-Reviewed Original ResearchConceptsDirect thrombin inhibitorAvailable direct thrombin inhibitorThrombin inhibitorsDegree of anticoagulationLife-threatening bleedsExperimental animal modelsSupportive careBleeding patientsCase reportClinical trialsFactor concentratesRoutine coagulationAnticoagulant effectPharmacologic propertiesAnimal modelsThrombin timeTransfusion productsPathology consultationAnticoagulationDrug concentrationsLaboratory assessmentNewer assaysDrug removalBleedingPrimary author
2011
Rapid clearance of transfused murine red blood cells is associated with recipient cytokine storm and enhanced alloimmunogenicity
Hendrickson JE, Hod EA, Cadwell CM, Eisenbarth SC, Spiegel DA, Tormey CA, Spitalnik SL, Zimring JC. Rapid clearance of transfused murine red blood cells is associated with recipient cytokine storm and enhanced alloimmunogenicity. Transfusion 2011, 51: 2445-2454. PMID: 21569043, PMCID: PMC3175302, DOI: 10.1111/j.1537-2995.2011.03162.x.Peer-Reviewed Original ResearchConceptsProinflammatory cytokine stormRed blood cellsHeat-treated red blood cellsFresh red blood cellsCytokine stormRBC clearanceAntigen expressionRapid clearanceBlood cellsAdverse transfusion outcomesFlow cytometric crossmatchChemoattractant protein-1Control red blood cellsDonor red blood cellsMurine red blood cellsStored red blood cellsTransgenic antigensCytometric crossmatchCytokine responsesRecipient miceInterleukin-6Transfusion outcomesHours posttransfusionHeat treatmentFourteen days