2024
Evolving Concepts in Pathophysiology, Screening, and Prevention of Type 1 Diabetes: Report of Diabetes Mellitus Interagency Coordinating Committee Workshop.
Greenbaum C, Nepom G, Wood-Heickman L, Wherrett D, DiMeglio L, Herold K, Krischer J. Evolving Concepts in Pathophysiology, Screening, and Prevention of Type 1 Diabetes: Report of Diabetes Mellitus Interagency Coordinating Committee Workshop. Diabetes 2024, 73: 1780-1790. PMID: 39167668, PMCID: PMC11493760, DOI: 10.2337/dbi24-0020.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, Monoclonal, HumanizedDiabetes Mellitus, Type 1HumansMass ScreeningUnited StatesConceptsType 1 diabetesClinical trialsType 1 Diabetes TrialNetEtiology of type 1 diabetesImmune Tolerance NetworkFood and Drug AdministrationU.S. Food and Drug AdministrationNational Institute of DiabetesDigestive and Kidney DiseasesMultiple immune pathwaysDisease-modifying therapiesMechanism of actionTherapeutic responsePrognostic markerKidney diseaseDrug AdministrationTrialNetClinical diagnosisImmune pathwaysDiabetesTeplizumabRegulatory approvalClinical carePathophysiologyDiseaseEarly Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials.
Jacobsen L, Cuthbertson D, Bundy B, Atkinson M, Moore W, Haller M, Russell W, Gitelman S, Herold K, Redondo M, Sims E, Wherrett D, Moran A, Pugliese A, Gottlieb P, Sosenko J, Ismail H. Early Metabolic Endpoints Identify Persistent Treatment Efficacy in Recent-Onset Type 1 Diabetes Immunotherapy Trials. Diabetes Care 2024, 47: 1048-1055. PMID: 38621411, PMCID: PMC11294635, DOI: 10.2337/dc24-0171.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultArea Under CurveC-PeptideChildDiabetes Mellitus, Type 1FemaleHumansImmunotherapyMaleRandomized Controlled Trials as TopicTreatment OutcomeConceptsC-peptide area-under-the-curveArea under the curveC-peptideRecent-onset type 1 diabetesTreatment efficacyEarly-phase clinical trialsC-peptide preservationPrimary end pointB cell functionDetect treatment efficacyType 1 diabetesPost hoc analysisRandomized controlled trialsImmune therapyImmunotherapy trialsMonths posttherapyClinical trialsTreatment effectsEnd pointsMetabolic indicesHoc analysisControlled trialsType 1 diabetes trialsMetabolic endpointsIntervention trials
2019
An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes
Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. New England Journal Of Medicine 2019, 381: 603-613. PMID: 31180194, PMCID: PMC6776880, DOI: 10.1056/nejmoa1902226.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAntibodies, Monoclonal, HumanizedCD3 ComplexChildDiabetes Mellitus, Type 1Disease ProgressionDouble-Blind MethodExanthemaFemaleGlucose Tolerance TestHLA-DR3 AntigenHLA-DR4 AntigenHumansLymphocyte CountLymphopeniaMaleMiddle AgedProportional Hazards ModelsT-LymphocytesYoung AdultConceptsType 1 diabetesClinical type 1 diabetesTeplizumab groupPlacebo groupOral glucose tolerance testInsulin-producing beta cellsDouble-blind trialChronic autoimmune diseaseGlucose tolerance testRelatives of patientsRate of diagnosisHigh-risk participantsTransient lymphopeniaAdverse eventsHazard ratioHLA-DR3HLA-DR4Median timeClinical progressionAutoimmune diseasesExogenous insulinCD3 antibodyT cellsTeplizumabClinical disease
2018
Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors
Stamatouli AM, Quandt Z, Perdigoto AL, Clark PL, Kluger H, Weiss SA, Gettinger S, Sznol M, Young A, Rushakoff R, Lee J, Bluestone JA, Anderson M, Herold KC. Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors. Diabetes 2018, 67: dbi180002. PMID: 29937434, PMCID: PMC6054443, DOI: 10.2337/dbi18-0002.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntineoplastic Agents, ImmunologicalAutoimmune DiseasesB7-H1 AntigenDiabetes Mellitus, Type 1Genetic Predisposition to DiseaseGenotypeHLA-DR4 AntigenHumansHypoglycemic AgentsInsulinInsulin SecretionIsoantibodiesKetosisModels, ImmunologicalNeoplasmsPancreasPancreatitisProgrammed Cell Death 1 ReceptorConceptsInsulin-dependent diabetesCheckpoint inhibitorsAdverse eventsHLA-DR4Classic type 1 diabetesPD-L1 checkpoint inhibitorsEvidence of pancreatitisImmune adverse eventsSolid organ cancersType 1 diabetesPeridiagnosis periodPositive autoantibodiesL1 antibodyInsulin-DependentHigh riskPatientsDiabetesCancerInhibitorsKetoacidosisAutoimmuneAutoantibodiesPancreatitisComplicationsSyndrome
2015
β Cell death and dysfunction during type 1 diabetes development in at-risk individuals
Herold KC, Usmani-Brown S, Ghazi T, Lebastchi J, Beam CA, Bellin MD, Ledizet M, Sosenko JM, Krischer JP, Palmer JP. β Cell death and dysfunction during type 1 diabetes development in at-risk individuals. Journal Of Clinical Investigation 2015, 125: 1163-1173. PMID: 25642774, PMCID: PMC4362259, DOI: 10.1172/jci78142.Peer-Reviewed Original ResearchMeSH KeywordsCell DeathChildDiabetes Mellitus, Type 1Disease ProgressionDNA MethylationGlucose IntoleranceHumansInsulinInsulin-Secreting CellsProspective StudiesRiskConceptsUnmethylated INS DNAINS DNARisk individualsType 1 diabetes developmentCell killingT1D-associated autoimmunityUnmethylated insulin DNADiagnosis of T1DHigh-risk subjectsAmerican Diabetes AssociationHealthy control subjectsJuvenile Diabetes Research FoundationPrimary pathologic processType 1 diabetesCell deathΒ-cell deathNonprogressor groupPeridiagnosis periodTrialNet PathwayBlood testsDiabetes AssociationDiabetes developmentIslet autotransplantMetabolic decompensationControl subjects
2012
Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients
Waldron-Lynch F, Henegariu O, Deng S, Preston-Hurlburt P, Tooley J, Flavell R, Herold KC. Teplizumab Induces Human Gut-Tropic Regulatory Cells in Humanized Mice and Patients. Science Translational Medicine 2012, 4: 118ra12. PMID: 22277969, PMCID: PMC4131554, DOI: 10.1126/scitranslmed.3003401.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, Monoclonal, HumanizedCD3 ComplexCell MovementDiabetes Mellitus, Type 1Forkhead Transcription FactorsGastrointestinal TractHumansHypoglycemic AgentsInterleukin-10Intestine, SmallL-SelectinMiceMucous MembraneNatalizumabOligonucleotide Array Sequence AnalysisReceptors, CCR6T-Lymphocytes, RegulatoryConceptsHumanized micePeripheral circulationSmall intestineType 1 diabetes mellitusNovel immunologic mechanismIL-10 expressionTreatment of patientsType 1 diabetesSecondary lymph organsHuman immune cellsT cell migrationMechanism of actionGut-tropicImmunologic mechanismsRegulatory cellsDiabetes mellitusImmune therapyInterleukin-10Immune cellsRegulatory cytokinesClinical trialsPreclinical modelsClinical studiesT cellsHuman hematopoietic stem cells