2024
The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases
Sumida T, Cheru N, Hafler D. The regulation and differentiation of regulatory T cells and their dysfunction in autoimmune diseases. Nature Reviews Immunology 2024, 24: 503-517. PMID: 38374298, PMCID: PMC11216899, DOI: 10.1038/s41577-024-00994-x.Peer-Reviewed Original ResearchTreg cell dysfunctionTreg cellsAutoimmune diseasesCell dysfunctionSuppressive function of Treg cellsDifferentiation of regulatory T cellsFunction of Treg cellsDiscovery of Foxp3Foxp3-independent mechanismsTreg cell suppressionRegulatory T cellsTreg cell functionTranscription factor Foxp3Systemic lupus erythematosusRegulate immune responsesInflammatory bowel diseaseFOXP3 mutationsFoxp3-dependentSystemic autoinflammationRegulatory TIPEX syndromeCell lineage determinationT cellsTregsLupus erythematosus
2021
A phase 1b study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO).
Dumbrava E, Dougan M, Gupta S, Cappelli L, Katsumoto T, Rahma O, Painter J, Wang Y, Suarez-Almazor M, Reid P, Wesley S, Hafler D, Bingham C, Warner B, Chung L, Ott P, Kluger H, Khosroshahi A, Tawbi H, Sharon E. A phase 1b study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO). Journal Of Clinical Oncology 2021, 39: tps2676-tps2676. DOI: 10.1200/jco.2021.39.15_suppl.tps2676.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsDisease-specific cohortsAutoimmune disordersAdverse eventsAdvanced malignanciesAnti-PD-1/PD-L1 antibodiesPre-existing autoimmune disordersAnti-PD1 monoclonal antibodiesImpact of nivolumabPhase 1b studyKey secondary endpointPhase Ib studySerious adverse eventsDose-limiting toxicityInflammatory bowel diseasePD-L1 antibodiesSeverity IndexSystemic lupus erythematosusDysfunctional immune systemClinical Trials NetworkTissue-based biomarkersSpecific eligibility criteriaICI therapyPrimary endpointSecondary endpoints
2020
A phase Ib study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO).
Ileana Dumbrava E, Suarez-Almazor M, Painter J, Johanns T, Dougan M, Cappelli L, Bingham C, Wang Y, Gupta S, Warner B, Rahma O, Naidoo J, Ott P, Hafler D, Kluger H, Khosroshahi A, Katsumoto T, Kummar S, Sharon E, Tawbi H. A phase Ib study of nivolumab in patients with autoimmune disorders and advanced malignancies (AIM-NIVO). Journal Of Clinical Oncology 2020, 38: tps3158-tps3158. DOI: 10.1200/jco.2020.38.15_suppl.tps3158.Peer-Reviewed Original ResearchImmune checkpoint inhibitorsAnti-PD-1/PD-L1 antibodiesPhase Ib studyPD-L1 antibodiesAutoimmune disordersAdvanced malignanciesDisease-specific cohortsAdverse eventsIb studyPre-existing autoimmune disordersImpact of nivolumabRisk of flareKey secondary endpointSerious adverse eventsBest objective responseDose-limiting toxicityInflammatory bowel diseaseSeverity IndexSystemic lupus erythematosusAnti-PD1 antibodyClinical Trials NetworkTissue-based biomarkersSpecific eligibility criteriaICI therapyCheckpoint inhibitors
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 period
2011
Pervasive Sharing of Genetic Effects in Autoimmune Disease
Cotsapas C, Voight BF, Rossin E, Lage K, Neale BM, Wallace C, Abecasis GR, Barrett JC, Behrens T, Cho J, De Jager PL, Elder JT, Graham RR, Gregersen P, Klareskog L, Siminovitch KA, van Heel DA, Wijmenga C, Worthington J, Todd JA, Hafler DA, Rich SS, Daly MJ, . Pervasive Sharing of Genetic Effects in Autoimmune Disease. PLOS Genetics 2011, 7: e1002254. PMID: 21852963, PMCID: PMC3154137, DOI: 10.1371/journal.pgen.1002254.Peer-Reviewed Original ResearchConceptsSingle nucleotide polymorphismsSystemic lupus erythematosusImmune-mediated diseasesType 1 diabetesGenetic risk factorsMajor histocompatibility locusCommon autoimmuneCommon single nucleotide polymorphismsLupus erythematosusCrohn's diseaseRheumatoid arthritisClinical evidenceMultiple sclerosisAutoimmune diseasesRisk single nucleotide polymorphismsCeliac diseaseInflammatory diseasesRisk factorsMeta-AnalysisDisease riskDiseaseHistocompatibility locusUnderlying mechanismGenetic associationNucleotide polymorphisms
2009
Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases
Rioux J, Goyette P, Vyse T, Hammarström L, Fernando M, Green T, De Jager P, Foisy S, Wang J, de Bakker P, Leslie S, McVean G, Padyukov L, Alfredsson L, Annese V, Hafler D, Pan-Hammarström Q, Matell R, Sawcer S, Compston A, Cree B, Mirel D, Daly M, Behrens T, Klareskog L, Gregersen P, Oksenberg J, Hauser S. Mapping of multiple susceptibility variants within the MHC region for 7 immune-mediated diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 18680-18685. PMID: 19846760, PMCID: PMC2773992, DOI: 10.1073/pnas.0909307106.Peer-Reviewed Original ResearchConceptsAutoimmune diseasesSystemic lupus erythematosusSelective IgA deficiencyStrong susceptibility locusNon-HLA genesMHC regionLupus erythematosusMyasthenia gravisUlcerative colitisCrohn's diseaseRheumatoid arthritisIgA deficiencyMultiple sclerosisMultiple susceptibility variantsMHC associationsDiseaseAppropriate control samplesPrimary association signalStrong linkage disequilibriumIndependent association signalsHuman MHCSusceptibility variantsSusceptibility lociAssociation signalsMost studies
2006
The role of inflammatory bowel disease susceptibility loci in multiple sclerosis and systemic lupus erythematosus
De Jager PL, Graham R, Farwell L, Sawcer S, Richardson A, Behrens TW, Compston A, Hafler DA, Kere J, Vyse TJ, Rioux JD. The role of inflammatory bowel disease susceptibility loci in multiple sclerosis and systemic lupus erythematosus. Genes & Immunity 2006, 7: 327-334. PMID: 16642031, DOI: 10.1038/sj.gene.6364303.Peer-Reviewed Original ResearchMeSH KeywordsChromosomes, Human, Pair 5ExonsGenetic Predisposition to DiseaseHumansInflammatory Bowel DiseasesIntracellular Signaling Peptides and ProteinsLupus Erythematosus, SystemicMembrane ProteinsMultiple SclerosisNod2 Signaling Adaptor ProteinPolymorphism, Single NucleotideTumor Suppressor ProteinsConceptsSystemic lupus erythematosusInflammatory bowel diseaseMultiple sclerosisRisk allelesLupus erythematosusInflammatory diseasesCases of SLERisk of SLECARD15/NOD2 geneGeneral susceptibility locusIBD risk allelesChronic inflammatory diseaseIBD5 locusComplex inflammatory diseaseInflammatory bowel disease susceptibility lociEvidence of associationLupus nephritisBowel diseaseSLE subjectsPooled analysisCARD15 geneSusceptibility lociNOD2 geneDiseaseErythematosus
2005
Evaluating the role of the 620W allele of protein tyrosine phosphatase PTPN22 in Crohn's disease and multiple sclerosis
De Jager PL, Sawcer S, Waliszewska A, Farwell L, Wild G, Cohen A, Langelier D, Bitton A, Compston A, Hafler DA, Rioux JD. Evaluating the role of the 620W allele of protein tyrosine phosphatase PTPN22 in Crohn's disease and multiple sclerosis. European Journal Of Human Genetics 2005, 14: 317-321. PMID: 16391555, DOI: 10.1038/sj.ejhg.5201548.Peer-Reviewed Original ResearchMeSH KeywordsAllelesCanadaCase-Control StudiesCrohn DiseaseGene FrequencyGenetic Predisposition to DiseaseGenotypeHumansInflammationModels, StatisticalMultiple SclerosisOdds RatioPolymorphism, GeneticProtein Tyrosine Phosphatase, Non-Receptor Type 1Protein Tyrosine Phosphatase, Non-Receptor Type 22Protein Tyrosine PhosphatasesRiskUnited KingdomConceptsSystemic lupus erythematosusCases of CDCrohn's diseaseMultiple sclerosisPTPN22 620W alleleAutoimmune thyroiditisRheumatoid arthritisInflammatory diseasesEvidence of associationCases of MSProtein tyrosine phosphatase PTPN22Chronic inflammatory diseaseType 1 diabetesTyrosine phosphatase PTPN22PTPN22 alleleLupus erythematosusPooled analysisControl subjectsModest odds ratiosOdds ratioDiseaseRisk allelesPhosphatase PTPN22SclerosisPossible role
1989
MS: a CNS and systematic autoimmune disease
Hafler D, Weiner H. MS: a CNS and systematic autoimmune disease. Trends In Immunology 1989, 10: 104-107. PMID: 2472810, DOI: 10.1016/0167-5699(89)90236-3.Peer-Reviewed Original ResearchConceptsPeripheral immune compartmentCentral nervous systemImmune compartmentMultiple sclerosisImmunoregulatory defectsMS patientsAutoimmune diseasesCNS inflammatory responsesTotal lymphoid irradiationProgressive multiple sclerosisT-cell abnormalitiesB cell hyperactivitySystemic lupus erythematosusT cell functionSystematic autoimmune diseaseActivated T cellsLymphoid irradiationDisease activityImmune abnormalitiesSystemic treatmentLupus erythematosusRheumatoid arthritisPeripheral bloodInflammatory diseasesInflammatory response