2025
Monocyte/macrophage-derived interleukin-15 mediates the pro-inflammatory phenotype of CD226+ B cells in type 1 diabetes
Li J, Liang X, Zhao M, Luo W, Huang J, Xiao Y, Huang J, Zhao B, Zhou Z. Monocyte/macrophage-derived interleukin-15 mediates the pro-inflammatory phenotype of CD226+ B cells in type 1 diabetes. EBioMedicine 2025, 120: 105946. PMID: 40957221, PMCID: PMC12466144, DOI: 10.1016/j.ebiom.2025.105946.Peer-Reviewed Original ResearchGenome-wide association studiesAutoimmune-mediated destructionB cellsPro-inflammatory phenotypeType 1 diabetesNOD miceT cellsIL-15T1D patientsInterleukin-15Anti-IL-15 monoclonal antibodyCD8<sup>+</sup> T cellsDisease onsetInflammatory responseAnti-CD3 monoclonal antibodyNatural Science FoundationDestruction of pancreatic B-cellsAnti-IL-15B-cell axisMonoclonal antibodiesSusceptibility to several autoimmune diseasesProduction of pro-inflammatory cytokinesIL-15 signalingSeveral autoimmune diseasesDevelopment of T1D
2023
Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study
Hu J, Ding J, Li X, Li J, Zheng T, Xie L, Li C, Tang Y, Guo K, Huang J, Liu S, Yan J, Peng W, Hou C, Wen L, Xu A, Zhou Z, Xiao Y. Distinct signatures of gut microbiota and metabolites in different types of diabetes: a population-based cross-sectional study. EClinicalMedicine 2023, 62: 102132. PMID: 37593224, PMCID: PMC10430172, DOI: 10.1016/j.eclinm.2023.102132.Peer-Reviewed Original ResearchAdult-onset T1DHealthy controlsGut microbiotaT1D patientsShort-chain fatty acid-producing bacteriaPopulation-based cross-sectional studyGut microbial alterationsRecent epidemiological dataType 1 diabetesCross-sectional studyT2D patientsIntestinal disturbancesDifferential diagnosisSerum metabolitesEpidemiological dataPatientsStudy subjectsT1DDiabetesSignificant differencesAcid-producing bacteriaMicrobiotaMicrobial profilesNational Key ResearchMicrobial alterations
2021
Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology
Yang ML, Sodré FMC, Mamula MJ, Overbergh L. Citrullination and PAD Enzyme Biology in Type 1 Diabetes – Regulators of Inflammation, Autoimmunity, and Pathology. Frontiers In Immunology 2021, 12: 678953. PMID: 34140951, PMCID: PMC8204103, DOI: 10.3389/fimmu.2021.678953.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisPeptidylarginine deiminaseAutoimmune diseasesNeutrophil extracellular trap formationSystemic lupus erythematosusRole of neutrophilsPathogenesis of T1D.Different autoimmune diseasesType 1 diabetesExtracellular trap formationNovel therapeutic strategiesGenetic susceptibility factorsAmino acid citrullinePAD inhibitionNOD miceLupus erythematosusT1D patientsAutoimmune responseAutoreactive responsesDiabetes developmentMultiple sclerosisPathogenic roleInflammatory stressT cellsNeutrophil biology
2020
Inequities in Diabetic Ketoacidosis Among Patients With Type 1 Diabetes and COVID-19: Data From 52 US Clinical Centers
Ebekozien O, Agarwal S, Noor N, Albanese-O’Neill A, Wong JC, Seeherunvong T, Sanchez J, DeSalvo D, Lyons SK, Majidi S, Wood JR, Acharya R, Aleppo G, Sumpter KM, Cymbaluk A, Shah NA, Van Name M, Cruz-Aviles L, Alonso GT, Gallagher MP, Sanda S, Feuer AJ, Cossen K, Rioles N, Jones NY, Kamboj MK, Hirsch IB. Inequities in Diabetic Ketoacidosis Among Patients With Type 1 Diabetes and COVID-19: Data From 52 US Clinical Centers. The Journal Of Clinical Endocrinology & Metabolism 2020, 106: 1755-1762. PMID: 33410917, PMCID: PMC7928931, DOI: 10.1210/clinem/dgaa920.Peer-Reviewed Original ResearchConceptsNH Black patientsLaboratory-confirmed COVID-19NH-White patientsDiabetic ketoacidosisType 1 diabetesNH blacksBlack patientsNH whitesWhite patientsHispanic patientsPotential confoundersLaboratory-confirmed coronavirus disease 2019COVID-19Multivariable logistic regression analysisUS clinical centersCross-sectional studyCOVID-19 infectionCoronavirus disease 2019Logistic regression analysisRace/ethnicity groupsMedian HbA1cSerious complicationsDKA eventsPatient factorsT1D patients
2019
Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity
Stathopoulos P, Chastre A, Waters P, Irani S, Fichtner ML, Benotti ES, Guthridge JM, Seifert J, Nowak RJ, Buckner JH, Holers VM, James JA, Hafler DA, O’Connor K. Autoantibodies against Neurologic Antigens in Nonneurologic Autoimmunity. The Journal Of Immunology 2019, 202: ji1801295. PMID: 30824481, PMCID: PMC6452031, DOI: 10.4049/jimmunol.1801295.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusRheumatoid arthritisControl cohortNeuromyelitis optica spectrum disorderSurface AgOptica spectrum disorderMyelin oligodendrocyte glycoproteinHealthy donor seraType 1 diabetesB cell toleranceNeurologic autoimmunitySLE patientsLupus erythematosusSuch autoantibodiesT1D patientsAutoimmune diseasesHigh titer AbsOligodendrocyte glycoproteinSystemic autoimmunityDonor seraLarge cohortRare caseAutoantibodiesAquaporin-4Cell toleranceLatent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients
James JA, Chen H, Young KA, Bemis EA, Seifert J, Bourn RL, Deane KD, Demoruelle MK, Feser M, O'Dell JR, Weisman MH, Keating RM, Gaffney PM, Kelly JA, Langefeld CD, Harley JB, Robinson W, Hafler DA, O'Connor KC, Buckner J, Guthridge JM, Norris JM, Holers VM. Latent autoimmunity across disease-specific boundaries in at-risk first-degree relatives of SLE and RA patients. EBioMedicine 2019, 42: 76-85. PMID: 30952617, PMCID: PMC6491794, DOI: 10.1016/j.ebiom.2019.03.063.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusFirst-degree relativesGenetic risk scoreRA patientsRheumatoid arthritisSLE patientsT1D patientsAutoantibody-positive systemic lupus erythematosusRisk first-degree relativesOrgan-specific autoimmune diseasesType 1 diabetes patientsAutoimmune disease preventionAnti-tissue transglutaminaseDisease-associated autoantibodiesDisease prevention studiesUnaffected first-degree relativesCross-sectional studyLatent autoimmunityLupus erythematosusAutoimmune diseasesDiabetes patientsPrevention StudyRisk scoreAutoimmunityPreclinical periodNoninvasive diagnosis of recurrent autoimmune type 1 diabetes after islet cell transplantation
Korutla L, Rickels MR, Hu RW, Freas A, Reddy S, Habertheuer A, Harmon J, Korutla V, Ram C, Naji A, Vallabhajosyula P. Noninvasive diagnosis of recurrent autoimmune type 1 diabetes after islet cell transplantation. American Journal Of Transplantation 2019, 19: 1852-1858. PMID: 30801971, PMCID: PMC7043773, DOI: 10.1111/ajt.15322.Peer-Reviewed Original ResearchConceptsIslet cell transplantationAutoimmune type 1 diabetesType 1 diabetesCell transplantationT1D autoimmunityNoninvasive diagnosisPancreatic β-cell injuryGlutamic acid decarboxylase 65Time-matched analysisΒ-cell injuryTransplanted β-cellsHyperglycemia onsetIslet injuryRecurrent autoimmunityHypoglycemic unawarenessTime-specific increaseIslet autoantigensCurative therapyT1D patientsImmunologic rejectionExogenous insulinInjury typeControl subjectsIslet transplantationDonor islets
2018
Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes
Huang J, Xiao Y, Zheng P, Zhou W, Wang Y, Huang G, Xu A, Zhou Z. Distinct neutrophil counts and functions in newly diagnosed type 1 diabetes, latent autoimmune diabetes in adults, and type 2 diabetes. Diabetes/Metabolism Research And Reviews 2018, 35: e3064. PMID: 30123986, DOI: 10.1002/dmrr.3064.Peer-Reviewed Original ResearchConceptsNeutrophil countType 1 diabetesT1D patientsNeutrophil numbersPhagocytosis rateTitres of autoantibodiesΒ-cell antigensΒ-cell autoimmunityChemokine receptor expressionType 2 diabetesMigration of neutrophilsLADA patientsPositive autoantibodiesAutoimmune diabetesChemokine levelsCD62L expressionT2D patientsClinical parametersNeutrophil migrationHealthy controlsReceptor expressionAnimal modelsDiabetesPatientsDifferent subtypesIdentification and Analysis of Islet Antigen–Specific CD8+ T Cells with T Cell Libraries
Ogura H, Preston-Hurlburt P, Perdigoto AL, Amodio M, Krishnaswamy S, Clark P, Yu H, Egli D, Fouts A, Steck AK, Herold KC. Identification and Analysis of Islet Antigen–Specific CD8+ T Cells with T Cell Libraries. The Journal Of Immunology 2018, 201: 1662-1670. PMID: 30082321, PMCID: PMC6449153, DOI: 10.4049/jimmunol.1800267.Peer-Reviewed Original ResearchConceptsAg-specific T cellsT cellsT cell librariesIslet antigen-specific CD8Antigen-specific CD8Class I MHC tetramersAg-specific cellsT cell subsetsHealthy control subjectsType 1 diabetesT cell clonotypesTCR gene sequencesAutoreactive CD8Reactive CD8T1D patientsCell subsetsMHC tetramersPeripheral bloodControl subjectsHealthy controlsCell clonotypesCD8Activation phenotypePatientsTCR sequencesSuppression of Ketogenesis in Type 1 Diabetes Is Not Delayed by SGLT2 Inhibitor Therapy
SIEBEL S, PATEL N, GALDERISI A, CARRIA L, TAMBORLANE W, SHERR J. Suppression of Ketogenesis in Type 1 Diabetes Is Not Delayed by SGLT2 Inhibitor Therapy. Diabetes 2018, 67 DOI: 10.2337/db18-117-lb.Peer-Reviewed Original ResearchPlasma glucoseSGLT2i useBHB levelsMedtronic MiniMedBoehringer Ingelheim GmbHSGLT2 inhibitor therapyInterruption studiesRapid-acting insulinType 1 diabetesRisk of DKABasal insulin infusionEli LillySuppression of ketogenesisCanagliflozin therapyRescue doseSGLT2i therapySGLT2i treatmentBasal insulinInhibitor therapySGLT2 inhibitorsT1D patientsAdjunctive agentsMetabolic decompensationInsulin infusionJanssen PharmaceuticalsT1D and T2D Youth in the Pediatric Diabetes Consortium (PDC) Registries—Comparing Clinical Characteristics and Glycemic Control
TAMBORLANE W, CHENG P, GAL R, KOLLMAN C, VAN NAME M, LYNCH J, NELSON B. T1D and T2D Youth in the Pediatric Diabetes Consortium (PDC) Registries—Comparing Clinical Characteristics and Glycemic Control. Diabetes 2018, 67 DOI: 10.2337/db18-1340-p.Peer-Reviewed Original ResearchTarget HbA1c levelT2D youthHbA1c levelsMedtronic MiniMedResidual endogenous insulin secretionHigher mean HbA1c levelsBoehringer Ingelheim GmbHMean HbA1c levelEndogenous insulin secretionOverweight/obesePoor diabetes outcomesChi-square testMann-Whitney UBoehringer Ingelheim PharmaceuticalsT2D durationClinical characteristicsInsulin therapyGlycemic controlT1D patientsDiabetes careDiabetes outcomesRisk factorsC-peptideInsulin secretionLogistic regression
2017
Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study
Patel NS, Van Name MA, Cengiz E, Carria LR, Weinzimer SA, Tamborlane WV, Sherr JL. Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study. Diabetes Technology & Therapeutics 2017, 19: 618-622. PMID: 29068709, PMCID: PMC5689123, DOI: 10.1089/dia.2017.0267.Peer-Reviewed Original ResearchConceptsSodium-glucose cotransporter 2 inhibitorsPlasma glucoseType 1 diabetesDiabetic ketoacidosisFree fatty acidsCANA treatmentBasal insulinGlucagon levelsMetabolic decompensationPlasma insulinInfusion site problemsCotransporter 2 inhibitorsBaseline plasma glucoseFailure of patientsBasal insulin infusionAdjunctive treatmentRate of ketogenesisSGLT2 inhibitorsT1D patientsT1D participantsInsulin infusionMagnitude of increasePG levelsSuspension studiesΒ-hydroxybutyrate
2016
The Receptor for Advanced Glycation Endproducts Drives T Cell Survival and Inflammation in Type 1 Diabetes Mellitus
Durning SP, Preston-Hurlburt P, Clark PR, Xu D, Herold KC, Group T. The Receptor for Advanced Glycation Endproducts Drives T Cell Survival and Inflammation in Type 1 Diabetes Mellitus. The Journal Of Immunology 2016, 197: 3076-3085. PMID: 27655844, PMCID: PMC5101164, DOI: 10.4049/jimmunol.1600197.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAsymptomatic DiseasesCD8-Positive T-LymphocytesCell SurvivalCells, CulturedChildDiabetes Mellitus, Type 1Disease ProgressionFemaleGene Expression ProfilingHumansImmunologic MemoryInflammationLymphocyte ActivationMaleReceptor for Advanced Glycation End ProductsRiskSignal TransductionUp-RegulationYoung AdultConceptsDamage-associated molecular patternsT cellsRAGE expressionT1D patientsInflammatory functionsRisk relativesCell activationHigh mobility group box 1Mobility group box 1Advanced glycated endproductsChronic autoimmune responseMolecular patternsEffector memory cellsHealthy control subjectsExpression of RAGEGroup box 1Type 1 diabetesAdvanced glycation endproductsT cell survivalAutoimmune responseAutoimmune diseasesControl subjectsDisease onsetRisk subjectsCell injury
2014
Interleukin-10+ Regulatory B Cells Arise Within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens
Kleffel S, Vergani A, Tezza S, Nasr M, Niewczas MA, Wong S, Bassi R, D’Addio F, Schatton T, Abdi R, Atkinson M, Sayegh MH, Wen L, Wasserfall CH, O’Connor K, Fiorina P. Interleukin-10+ Regulatory B Cells Arise Within Antigen-Experienced CD40+ B Cells to Maintain Tolerance to Islet Autoantigens. Diabetes 2014, 64: 158-171. PMID: 25187361, PMCID: PMC4274804, DOI: 10.2337/db13-1639.Peer-Reviewed Original ResearchConceptsIslet autoantigensB cellsT1D patientsInterleukin-10IL-10-producing B cellsHyperglycemic nonobese diabetic miceRegulatory B-cell responsesAutoreactive T cell responsesT cell-mediated responsesRole of BregsB-cell depletionRegulatory B cellsNonobese diabetic (NOD) miceNOD mouse modelT cell responsesB cell responsesType 1 diabetesB cell receptorAdoptive transferDiabetic miceAutoimmune diseasesHuman ILHyperglycemic miceMouse modelBregs
2013
Increased Brain Lactate Concentrations Without Increased Lactate Oxidation During Hypoglycemia in Type 1 Diabetic Individuals
De Feyter HM, Mason GF, Shulman GI, Rothman DL, Petersen KF. Increased Brain Lactate Concentrations Without Increased Lactate Oxidation During Hypoglycemia in Type 1 Diabetic Individuals. Diabetes 2013, 62: 3075-3080. PMID: 23715622, PMCID: PMC3749358, DOI: 10.2337/db13-0313.Peer-Reviewed Original ResearchConceptsBrain lactate concentrationBlood-brain barrierHypoglycemia unawarenessLactate concentrationT1D subjectsControl subjectsType 1 diabetic subjectsType 1 diabetic individualsBlood-borne lactateNondiabetic control subjectsPlasma lactate concentrationMonocarboxylic acid transportDiabetic subjectsHypoglycemic clampT1D patientsDiabetic individualsBrain metabolismBrain fuelBrain glutamateBrain energeticsHypoglycemiaPatientsMetabolic adaptationAcid transportSubjects
2012
Achievement of Target A1C Levels With Negligible Hypoglycemia and Low Glucose Variability in Youth With Short-Term Type 1 Diabetes and Residual β-Cell Function
Sherr J, Tamborlane WV, Xing D, Tsalikian E, Mauras N, Buckingham B, White NH, Arbelaez AM, Beck RW, Kollman C, Ruedy K. Achievement of Target A1C Levels With Negligible Hypoglycemia and Low Glucose Variability in Youth With Short-Term Type 1 Diabetes and Residual β-Cell Function. Diabetes Care 2012, 35: 817-820. PMID: 22323414, PMCID: PMC3308298, DOI: 10.2337/dc11-2190.Peer-Reviewed Original ResearchConceptsResidual β-cell functionΒ-cell functionSensor glucose levelsLower glucose variabilityType 1 diabetesGlucose levelsContinuous glucose monitoringT1D participantsGlucose variabilityMean sensor glucose levelPeak C-peptide levelsMixed meal tolerance testTarget A1C levelsC-peptide levelsLong-term T1DShort-term groupNondiabetic groupT1D groupA1c levelsT1D patientsLess hyperglycemiaNondiabetic individualsTolerance testInsulin treatmentHypoglycemia
2009
Monocytes from Patients with Type 1 Diabetes Spontaneously Secrete Proinflammatory Cytokines Inducing Th17 Cells
Bradshaw EM, Raddassi K, Elyaman W, Orban T, Gottlieb PA, Kent SC, Hafler DA. Monocytes from Patients with Type 1 Diabetes Spontaneously Secrete Proinflammatory Cytokines Inducing Th17 Cells. The Journal Of Immunology 2009, 183: 4432-4439. PMID: 19748982, PMCID: PMC2770506, DOI: 10.4049/jimmunol.0900576.Peer-Reviewed Original ResearchConceptsT cellsT1D subjectsImmune systemIL-17-secreting cellsIL-17-secreting T cellsProinflammatory cytokines IL-1betaProinflammatory T cellsEffector T cellsMemory T cellsLong-term patientsHealthy control subjectsCytokines IL-1betaIL-1R antagonistType 1 diabetesInnate immune systemAdaptive immune systemTh1/T1D patientsAutoimmune diseasesIL-6Control subjectsIL-1betaHealthy controlsMonocytesType 1
2007
Anti-CD20 Therapy in NOD Model of Type 1 Diabetes (131.26)
Hu C, Rodriguez D, Du W, Ahuja A, Wong F, Shlomchik M, Wen L. Anti-CD20 Therapy in NOD Model of Type 1 Diabetes (131.26). The Journal Of Immunology 2007, 178: s242-s242. DOI: 10.4049/jimmunol.178.supp.131.26.Peer-Reviewed Original ResearchTransgenic NOD miceB cellsNOD miceT cellsHuman CD20Pre-diabetic stageB-cell depletionRegulatory T cellsOnset of diabetesPathogenesis of T1DTGF-β productionType 1 diabetesAbstract B cellsCD20 therapyImportant APCsDiabetes onsetT1D patientsNOD modelAutoimmune diseasesCell depletionClinical trialsPreclinical studiesParticular therapyHuman studiesCD20
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