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
2016
The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations.
Kofler DM, Farkas A, von Bergwelt-Baildon M, Hafler DA. The Link Between CD6 and Autoimmunity: Genetic and Cellular Associations. Current Drug Targets 2016, 17: 651-65. PMID: 26844569, DOI: 10.2174/1389450117666160201105934.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteArthritis, RheumatoidAutoimmunityCD4-Positive T-LymphocytesCell Adhesion Molecules, NeuronalClinical Trials as TopicDisease Models, AnimalFetal ProteinsGenetic Predisposition to DiseaseHumansMultiple SclerosisPolymorphism, Single NucleotideConceptsMultiple sclerosisRheumatoid arthritisCentral nervous systemNervous systemSingle nucleotide polymorphismsDevelopment of MSTreatment of RARole of CD6T cell traffickingT cell functionGenetic risk factorsEndothelial cell barrierCD6 geneClinical responseGenetic associationClinical featuresAutoimmune diseasesSynovial cellsRisk factorsTumor necrosisSynovial fibroblastsPossible common mechanismT cellsT lymphocytesLeukocyte trafficking
2013
Specific peripheral B cell tolerance defects in patients with multiple sclerosis
Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P, Herold KC, Hafler DA, O’Connor K, Meffre E. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. Journal Of Clinical Investigation 2013, 123: 2737-2741. PMID: 23676463, PMCID: PMC3668812, DOI: 10.1172/jci68775.Peer-Reviewed Original ResearchConceptsB cell tolerance checkpointsB cell tolerance defectsMultiple sclerosisRheumatoid arthritisTolerance checkpointsB cellsPeripheral B cell tolerance checkpointsTolerance defectsAutoreactive B cell clonesMature naive B cellsType 1 diabetesAutoreactive B cellsB cell toleranceCentral nervous systemNaive B cellsB cell clonesB cell selectionEarly B cell developmentIPEX patientsMost patientsTreg functionHomeostatic proliferationAutoimmune diseasesPatientsHealthy individualsPhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis
Larman HB, Laserson U, Querol L, Verhaeghen K, Solimini NL, Xu GJ, Klarenbeek PL, Church GM, Hafler DA, Plenge RM, Nigrovic PA, De Jager PL, Weets I, Martens GA, O'Connor KC, Elledge SJ. PhIP-Seq characterization of autoantibodies from patients with multiple sclerosis, type 1 diabetes and rheumatoid arthritis. Journal Of Autoimmunity 2013, 43: 1-9. PMID: 23497938, PMCID: PMC3677742, DOI: 10.1016/j.jaut.2013.01.013.Peer-Reviewed Original ResearchConceptsType 1 diabetes patientsRheumatoid arthritis patientsMultiple sclerosis patientsLoss of tolerancePhage immunoprecipitation sequencingType 1 diabetesNeurological autoimmunitySeropositivity statusArthritis patientsRheumatoid arthritisSclerosis patientsMultiple sclerosisAutoimmune diseasesDiabetes patientsCerebrospinal fluidGeneral populationSynovial fluidHealthy seraPatientsSusceptible individualsAntibody specificityDiseaseReceptor specificitySerumHuman peptidome
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
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
2003
Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis
Cao D, Malmström V, Baecher‐Allan C, Hafler D, Klareskog L, Trollmo C. Isolation and functional characterization of regulatory CD25brightCD4+ T cells from the target organ of patients with rheumatoid arthritis. European Journal Of Immunology 2003, 33: 215-223. PMID: 12594850, DOI: 10.1002/immu.200390024.Peer-Reviewed Original ResearchConceptsT cellsRegulatory cellsRheumatoid arthritisSynovial fluidTarget organsSuch regulatory T cellsFunctional regulatory cellsInflamed knee jointsPathological T cellsActive rheumatoid arthritisAutologous T cellsRegulatory T cellsExperimental animal modelsPeripheral blood originAutoimmune manifestationsRA patientsAutoimmune diseasesPeripheral bloodSame patientAnimal modelsPatientsKnee jointBlood originDiseaseArthritis
1993
Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis
Trentham D, Dynesius-Trentham R, Orav E, Combitchi D, Lorenzo C, Sewell K, Hafler D, Weiner H. Effects of Oral Administration of Type II Collagen on Rheumatoid Arthritis. Science 1993, 261: 1727-1730. PMID: 8378772, DOI: 10.1126/science.8378772.Peer-Reviewed Original ResearchConceptsRheumatoid arthritisType II collagenT cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseChicken type II collagenII collagenActive rheumatoid arthritisDouble-blind trialOral tolerizationTender jointsTolerization approachComplete remissionSwollen jointsClinical efficacySynovial diseaseAutoimmune diseasesPotential autoantigensOral administrationT cellsArthritisSide effectsAnimal modelsDiseaseCollagen groupPatientsThe development of antigen specific therapies for autoimmune diseases; investigations in multiple sclerosis as a paradigm for rheumatoid arthritis.
Hafler DA, Zhang JW, LaSalle J, Donnelly C, Weiner HL, Wucherpfeffnig K. The development of antigen specific therapies for autoimmune diseases; investigations in multiple sclerosis as a paradigm for rheumatoid arthritis. Clinical And Experimental Rheumatology 1993, 11 Suppl 8: s39-40. PMID: 7686832.Peer-Reviewed Original Research
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