2021
Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children
Ramaswamy A, Brodsky NN, Sumida TS, Comi M, Asashima H, Hoehn KB, Li N, Liu Y, Shah A, Ravindra NG, Bishai J, Khan A, Lau W, Sellers B, Bansal N, Guerrerio P, Unterman A, Habet V, Rice AJ, Catanzaro J, Chandnani H, Lopez M, Kaminski N, Dela Cruz CS, Tsang JS, Wang Z, Yan X, Kleinstein SH, van Dijk D, Pierce RW, Hafler DA, Lucas CL. Immune dysregulation and autoreactivity correlate with disease severity in SARS-CoV-2-associated multisystem inflammatory syndrome in children. Immunity 2021, 54: 1083-1095.e7. PMID: 33891889, PMCID: PMC8043654, DOI: 10.1016/j.immuni.2021.04.003.Peer-Reviewed Original ResearchConceptsMIS-C patientsDisease severityInflammatory syndromeTCR repertoireSARS-CoV-2-associated multisystem inflammatory syndromeAsymptomatic SARS-CoV-2 infectionSARS-CoV-2 infectionAdult COVID-19Post-infectious complicationsMultisystem inflammatory syndromeCytotoxicity genesHealthy pediatricImmune dysregulationMemory TActive infectionMyeloid dysfunctionPatientsSingle-cell RNA sequencingFlow cytometrySerum proteomicsRepertoire analysisElevated expressionSeverityAlarminsCOVID-19
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 ResearchMeSH KeywordsAutoantibodiesAutoantigensAutoimmune DiseasesB-LymphocytesFemaleHEK293 CellsHumansMaleMiddle AgedNerve Tissue ProteinsConceptsSystemic 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
Evaluation of KIR4.1 as an Immune Target in Multiple Sclerosis
Chastre A, Hafler DA, O'Connor KC. Evaluation of KIR4.1 as an Immune Target in Multiple Sclerosis. New England Journal Of Medicine 2016, 374: 1495-1496. PMID: 27074083, PMCID: PMC4918464, DOI: 10.1056/nejmc1513302.Peer-Reviewed Original Research
2013
Protein array–based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis
Querol L, Clark PL, Bailey MA, Cotsapas C, Cross AH, Hafler DA, Kleinstein SH, Lee JY, Yaari G, Willis SN, O'Connor KC. Protein array–based profiling of CSF identifies RBPJ as an autoantigen in multiple sclerosis. Neurology 2013, 81: 956-963. PMID: 23921886, PMCID: PMC3888197, DOI: 10.1212/wnl.0b013e3182a43b48.Peer-Reviewed Original ResearchConceptsCSF of patientsMultiple sclerosisNeurologic diseaseEpstein-Barr virus infectionImmunoglobulin GElevated immunoglobulin GInflammatory neurologic diseasesSubset of patientsLarger validation cohortRecombination signal binding proteinImmunoglobulin kappa J regionCSF autoantibodiesValidation cohortControl subjectsSerum reactivityAutoantigen candidatesHigh prevalenceVirus infectionPatientsAutoantibodiesCSFSclerosisArray-based profilingDiseaseELISASerum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis
Van Haren K, Tomooka BH, Kidd BA, Banwell B, Bar-Or A, Chitnis T, Tenembaum SN, Pohl D, Rostasy K, Dale RC, O’Connor K, Hafler DA, Steinman L, Robinson WH. Serum autoantibodies to myelin peptides distinguish acute disseminated encephalomyelitis from relapsing– remitting multiple sclerosis. Multiple Sclerosis Journal 2013, 19: 1726-1733. PMID: 23612879, PMCID: PMC4411183, DOI: 10.1177/1352458513485653.Peer-Reviewed Original ResearchConceptsAcute disseminated encephalomyelitisMyelin basic proteinDisseminated encephalomyelitisMyelin peptidesMultiple sclerosisIgM autoantibodiesIsotype-specific secondary antibodiesPediatric acute disseminated encephalomyelitisRelapsing-remitting multiple sclerosisPediatric multiple sclerosisProteolipid proteinMicroarrays softwareBasic proteinMyelin antigensLaboratory featuresPeptide autoantibodiesMS seraSerum autoantibodiesIgG autoantibodiesAutoantibody biomarkersSerum IgGOligodendrocyte-specific proteinAutoantibody reactivityAdult MSAutoantibodiesPhIP-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
Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease
Dominguez-Villar M, Baecher-Allan CM, Hafler DA. Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease. Nature Medicine 2011, 17: 673-675. PMID: 21540856, PMCID: PMC3675886, DOI: 10.1038/nm.2389.Peer-Reviewed Original ResearchConceptsTreg cellsT helper type 1Regulatory T cellsT regulatory (Treg) cellsHelper type 1T helper typeHuman autoimmune diseasesHuman Treg cellsRegulatory cellsIL-12Multiple sclerosisAutoimmune diseasesPeripheral bloodHelper typeT cellsSuppressive activityType 1Functional plasticityConsiderable phenotypicCellsSclerosisIFNDiseaseMiceBlood
2009
Age-Dependent B Cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis
McLaughlin KA, Chitnis T, Newcombe J, Franz B, Kennedy J, McArdel S, Kuhle J, Kappos L, Rostasy K, Pohl D, Gagne D, Ness JM, Tenembaum S, O'Connor KC, Viglietta V, Wong SJ, Tavakoli NP, de Seze J, Idrissova Z, Khoury SJ, Bar-Or A, Hafler DA, Banwell B, Wucherpfennig KW. Age-Dependent B Cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis. The Journal Of Immunology 2009, 183: 4067-4076. PMID: 19687098, PMCID: PMC2795331, DOI: 10.4049/jimmunol.0801888.Peer-Reviewed Original ResearchConceptsMyelin oligodendrocyte glycoproteinMultiple sclerosisB cell autoimmunityCell autoimmunityMOG-AbNative myelin oligodendrocyte glycoproteinPediatric-onset multiple sclerosisEarly onsetSurface AgPediatric MS casesPediatric-onset MSPediatric multiple sclerosisAdult-onset patientsCNS white matterHuman CNS white matterYears of ageAdult-onset diseaseDifferent myelin proteinsImmunological mechanismsPediatric patientsSerum AbsSuch autoantibodiesOligodendrocyte glycoproteinDisease onsetGlial cells
2007
Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein
O'Connor KC, McLaughlin KA, De Jager PL, Chitnis T, Bettelli E, Xu C, Robinson WH, Cherry SV, Bar-Or A, Banwell B, Fukaura H, Fukazawa T, Tenembaum S, Wong SJ, Tavakoli NP, Idrissova Z, Viglietta V, Rostasy K, Pohl D, Dale RC, Freedman M, Steinman L, Buckle GJ, Kuchroo VK, Hafler DA, Wucherpfennig KW. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein. Nature Medicine 2007, 13: 211-217. PMID: 17237795, PMCID: PMC3429369, DOI: 10.1038/nm1488.Peer-Reviewed Original ResearchConceptsAcute disseminated encephalomyelitisMyelin oligodendrocyte glycoproteinMultiple sclerosisFluorescent-activated cell sortingRole of autoantibodiesExperimental autoimmune encephalomyelitisConformation-independent antibodiesDiscrimination of antibodiesMOG-specific autoantibodiesDisseminated encephalomyelitisMOG peptidesAutoimmune encephalomyelitisOligodendrocyte glycoproteinAutoantibody detectionTarget antigenAutoantibodiesMS casesELISA methodWestern blottingRadioimmunoassayAntibodiesEncephalomyelitisAntigen domainSensitive assayConformation-sensitive antibodies
2006
Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers
O’Connor K, Roy SM, Becker CH, Hafler DA, Kantor AB. Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers. Disease Markers 2006, 22: 213-225. PMID: 17124343, PMCID: PMC3851054, DOI: 10.1155/2006/670439.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAutoantibodiesBiomarkersHumansInflammationMultiple SclerosisNeurodegenerative DiseasesPhenotypeProteomicsConceptsMultiple sclerosisMagnetic resonance imagingPutative biomarkersComprehensive phenotypingMonitoring of progressionComponent expression levelsClinical evaluationCSF proteinAccurate biomarkersCerebrospinal fluid chemistryControl groupTherapeutic interventionsPatient careAccurate diagnosisResonance imagingDisease pathologyFurther evaluationBiomarkersPreliminary dataExpression levelsSclerosisDiagnosisCSFSingle testNovel assessment
2005
Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein
O’Connor K, Appel H, Bregoli L, Call ME, Catz I, Chan JA, Moore NH, Warren KG, Wong SJ, Hafler DA, Wucherpfennig KW. Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein. The Journal Of Immunology 2005, 175: 1974-1982. PMID: 16034142, PMCID: PMC4515951, DOI: 10.4049/jimmunol.175.3.1974.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAutoantibodiesBinding Sites, AntibodyCentral Nervous SystemDemyelinating Autoimmune Diseases, CNSFemaleFluoroimmunoassayHumansMaleMolecular Sequence DataMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRadioimmunoassaySolutionsConceptsMyelin oligodendrocyte glycoproteinMultiple sclerosisCNS diseaseOligodendrocyte glycoproteinCNS tissueChronic inflammatory CNS diseasesAutoantibody-mediated pathologyInflammatory CNS diseasesCentral nervous system tissueInflammatory CNS diseaseCases of encephalitisHigh-affinity autoantibodiesCases of subacuteNervous system tissueCNS parenchymaMOG autoantibodiesMS patientsOligodendrocyte lossMOG-AbCNS diseasesAutoantibodiesCerebrospinal fluidMOG proteinPostmortem casesControl tissuesMultiple sclerosis
Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher‐Allan C. Multiple sclerosis. Immunological Reviews 2005, 204: 208-231. PMID: 15790361, DOI: 10.1111/j.0105-2896.2005.00240.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsAnimalsAutoantibodiesCentral Nervous SystemGenetic VariationHumansImmunosuppression TherapyMultiple SclerosisT-LymphocytesConceptsMultiple sclerosisT cellsB cellsImmunopathology of MSCentral nervous system white matterNervous system white matterRegulatory T cellsHallmark of inflammationImmunosuppressive therapyAutoimmune processImmunomodulatory therapeuticsAnimal modelsMS researchWhite matterDisease pathologyClonal expansionDiseaseMajor histocompatibility complex (MHC) genesMolecular pathologyRNA expressionSclerosisInflammationTherapyPathologyComplex genetic diseases
2003
Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions
O'Connor KC, Chitnis T, Griffin DE, Piyasirisilp S, Bar-Or A, Khoury S, Wucherpfennig KW, Hafler DA. Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions. Journal Of Neuroimmunology 2003, 136: 140-148. PMID: 12620653, DOI: 10.1016/s0165-5728(03)00002-x.Peer-Reviewed Original ResearchConceptsMyelin basic proteinMultiple sclerosisCerebrospinal fluidSoluble myelin basic proteinSemple rabies vaccinePresence of autoantibodiesMultiple sclerosis patientsSera of patientsFraction of patientsAnti-MBP antibodiesHigh-affinity autoantibodiesBasic proteinMBP autoantibodiesRelevant autoantibodiesMS patientsSclerosis patientsAutoimmune diseasesHumoral responseRabies vaccineAutoantibodiesPatientsImmunodominant antigensSerumDiseaseSolid-phase assays
2001
Heterophile Antibodies Indicate Progression of Autoimmunity in Human Type 1 Diabetes Mellitus Before Clinical Onset
Orban T, Kent SC, Malik P, Milner JD, Schuster K, Jackson RA, Hafler DA. Heterophile Antibodies Indicate Progression of Autoimmunity in Human Type 1 Diabetes Mellitus Before Clinical Onset. Autoimmunity 2001, 34: 247-264. PMID: 11905851, DOI: 10.3109/08916930109014694.Peer-Reviewed Original ResearchConceptsHeterophile antibodiesType 1 diabetes autoimmunityType 1 diabetes mellitus patientsDiabetes mellitus patientsProgression of autoimmunityAntibody-positive seraType 1 diabetesFirst-degree relativesHuman type 1T cell growthAnti-human immunoglobulinDiabetes autoimmunitySerum cytokinesMellitus patientsClinical onsetAntibody presenceIL-4Degree relativesDisease progressionLower incidenceHigh riskHigh incidenceHeterophilic antibodiesAntibody activityAntibody reactivity
1988
Immunotherapy of multiple sclerosis
Weiner H, Hafler D. Immunotherapy of multiple sclerosis. Annals Of Neurology 1988, 23: 211-222. PMID: 3288084, DOI: 10.1002/ana.410230302.Peer-Reviewed Original ResearchConceptsMultiple sclerosisClinical trialsHelper/inducer cellsOnset of progressionMultiple sclerosis therapyNumber of relapsesPresent treatment modalitiesAntigen-specific cellsActivated T cellsImmune balanceImmunotherapeutic interventionsNonspecific immunosuppressionSclerosis therapyAcute attacksAutoimmune diseasesInducer cellsLymphocyte trafficTreatment modalitiesSuppressor influencesEarly treatmentT cellsEffective treatmentTherapeutic goalsImmunotherapyImmune system
1984
Autoimmunity following viral infection: demonstration of monoclonal antibodies against normal tissue following infection of mice with reovirus and demonstration of shared antigenicity between virus and lymphocytes
Tardieu M, Powers M, Hafler D, Hauser S, Weiner H. Autoimmunity following viral infection: demonstration of monoclonal antibodies against normal tissue following infection of mice with reovirus and demonstration of shared antigenicity between virus and lymphocytes. European Journal Of Immunology 1984, 14: 561-565. PMID: 6329771, DOI: 10.1002/eji.1830140614.Peer-Reviewed Original ResearchConceptsNormal tissuesMonoclonal antibodiesViral infectionOnly virusInfection of miceUninfected control animalsAdult C57BL/6 miceAutoreactive monoclonal antibodiesNS1 myeloma cellsReovirus type 3Reovirus type 1Autoimmune responseC57BL/6 miceLung tissueT lymphocytesImmune responseSplenic lymphocytesControl animalsEpendymal cellsViral determinantsMyeloma cellsType 1LymphocytesInfectionReovirus type