2023
Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity
Shinoda K, Li R, Rezk A, Mexhitaj I, Patterson K, Kakara M, Zuroff L, Bennett J, von Büdingen H, Carruthers R, Edwards K, Fallis R, Giacomini P, Greenberg B, Hafler D, Ionete C, Kaunzner U, Lock C, Longbrake E, Pardo G, Piehl F, Weber M, Ziemssen T, Jacobs D, Gelfand J, Cross A, Cameron B, Musch B, Winger R, Jia X, Harp C, Herman A, Bar-Or A. Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2207291120. PMID: 36634138, PMCID: PMC9934304, DOI: 10.1073/pnas.2207291120.Peer-Reviewed Original ResearchConceptsEarly disease activityDisease activityCD8 T cellsT cellsCD20 therapyPeripheral blood mononuclear cellsCellular immune profilesNew disease activityMS disease activityT cell poolMultiple sclerosis patientsAnti-inflammatory profileBlood mononuclear cellsTreatment-associated changesMultiparametric flow cytometryCentral nervous systemFurther dosingRepeat infusionsImmune profileMS patientsSclerosis patientsValidation cohortMononuclear cellsRelapse developmentImmune cascade
2016
Multiple sclerosis
Axisa PP, Hafler DA. Multiple sclerosis. Current Opinion In Neurology 2016, 29: 345-353. PMID: 27058221, PMCID: PMC7882195, DOI: 10.1097/wco.0000000000000319.Peer-Reviewed Original ResearchConceptsMultiple sclerosisGenome-wide association studiesAssociation studiesMultiple sclerosis (MS) etiologyMultiple sclerosis progressionMultiple sclerosis patientsHigh-throughput genetic analysisImmune cell functionNumerous candidate biomarkersWide association studyMechanisms of neurodegenerationImmunomodulatory treatmentSclerosis patientsClinical outcomesTreatment arsenalDisease progressionImmune regulationSclerosisNew biomarkersCandidate biomarkersPatient careGenetic variationGenetic analysisCell functionProgression
2013
PhIP-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
2012
An RNA Profile Identifies Two Subsets of Multiple Sclerosis Patients Differing in Disease Activity
Ottoboni L, Keenan BT, Tamayo P, Kuchroo M, Mesirov JP, Buckle GJ, Khoury SJ, Hafler DA, Weiner HL, De Jager PL. An RNA Profile Identifies Two Subsets of Multiple Sclerosis Patients Differing in Disease Activity. Science Translational Medicine 2012, 4: 153ra131. PMID: 23019656, PMCID: PMC3753678, DOI: 10.1126/scitranslmed.3004186.Peer-Reviewed Original ResearchConceptsGlatiramer acetateDisease activityPatient populationFirst-line disease-modifying treatmentsMultiple sclerosis (MS) patient populationPeripheral blood mononuclear cellsMS patient populationDisease-modifying treatmentsMultiple sclerosis patientsBlood mononuclear cellsSubset of subjectsDisease courseSclerosis patientsMS subjectsMononuclear cellsInflammatory eventsTreatment responseUntreated subjectsAdditional groupHigh expressionTranscriptional signatureSubjectsRNA profilesTreatmentTranscriptional profiles
2007
Protective and therapeutic role for αB-crystallin in autoimmune demyelination
Ousman SS, Tomooka BH, van Noort JM, Wawrousek EF, O’Conner K, Hafler DA, Sobel RA, Robinson WH, Steinman L. Protective and therapeutic role for αB-crystallin in autoimmune demyelination. Nature 2007, 448: 474-479. PMID: 17568699, DOI: 10.1038/nature05935.Peer-Reviewed Original Research
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
1999
Cross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein
Ausubel L, Bieganowska K, Hafler D. Cross-Reactivity of T-Cell Clones Specific for Altered Peptide Ligands of Myelin Basic Protein. Cellular Immunology 1999, 193: 99-107. PMID: 10202117, DOI: 10.1006/cimm.1998.1447.Peer-Reviewed Original ResearchConceptsT cell clonesT cellsSpecific T cell repertoireAutoreactive T cellsTh1-type cytokinesTh2-type cytokinesMultiple sclerosis patientsT cell repertoireAltered peptide ligandT cell receptor alphaPotential beneficial effectsTCR contact residuesMyelin basic proteinDownregulatory cytokinesSclerosis patientsIL-4IL-5Individual patientsReceptor alphaBeneficial effectsClonal expansionCytokinesPeptide ligandsSubstantial proliferationCross reactivity
1998
Pulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients
Takashima H, Smith D, Fukaura H, Khoury S, Hafler D, Weiner H. Pulse Cyclophosphamide Plus Methylprednisolone Induces Myelin-Antigen-Specific IL-4-Secreting T Cells in Multiple Sclerosis Patients. Clinical Immunology 1998, 88: 28-34. PMID: 9683547, DOI: 10.1006/clin.1998.4558.Peer-Reviewed Original ResearchConceptsIL-4-secreting T cellsUntreated MS patientsProgressive MS patientsT cell linesMS patientsIL-4 secretionMyelin basic proteinT cellsMultiple sclerosisMyelin antigensTetanus toxoidTh1-type autoimmune diseaseShort-term T cell linesCell linesPulse cyclophosphamide therapyTh2-type responseIL-4 productionMultiple sclerosis patientsIFN-gamma productionProteolipid proteinImmune deviationPulse cyclophosphamideCyclophosphamide therapySclerosis patientsAutoimmune diseases
1995
Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter
McLaurin J, Hafler D, Antel J. Reactivity of normal T-cell lines to MBP isolated from normal and multiple sclerosis white matter. Journal Of The Neurological Sciences 1995, 128: 205-211. PMID: 7537795, DOI: 10.1016/0022-510x(94)00224-c.Peer-Reviewed Original ResearchConceptsT cell linesMyelin basic proteinMS white matterCentral nervous systemWhite matterMBP preparationsMS brainsPeripheral bloodRegion of MBPMultiple sclerosis white matterMBP-reactive T cell linesReactive T cell linesHuman T cell clonesT cell reactivityMultiple sclerosis patientsAutologous peripheral bloodNormal T-cell linesConcentration-response curvesT cell clonesAdult white matterHuman myelin basic proteinBasic proteinMS patientsSclerosis patientsMononuclear cellsTherapy for Multiple Sclerosis
Weiner H, Hohol M, Khoury S, Dawson D, Hafler D. Therapy for Multiple Sclerosis. Neurologic Clinics 1995, 13: 173-196. PMID: 7739502, DOI: 10.1016/s0733-8619(18)30066-5.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCell-mediated autoimmune diseaseAccumulation of disabilityMultiple sclerosis patientsSymptomatic therapySclerosis patientsAutoimmune responseCentral nervous system myelinAutoimmune diseasesNonspecific modulationImmune systemSclerosisSystem myelinTherapyImmunotherapyPatientsDiseaseMyelin
1994
Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis.
Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA. Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. Journal Of Experimental Medicine 1994, 179: 973-984. PMID: 7509366, PMCID: PMC2191414, DOI: 10.1084/jem.179.3.973.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsFrequency of MBPMBP-reactive T cell linesMBP-reactive T cellsMyelin basic proteinT cellsCerebrospinal fluidT cell linesMS patientsProteolipid proteinPLP-reactive T cellsNormal individualsFrequency of interleukinAutoreactive T cellsPathogenesis of MSMultiple sclerosis patientsIL-2-responsive cellsRIL-2 stimulationCentral nervous systemCell linesBasic proteinSclerosis patientsMultiple sclerosisPeripheral bloodPathogenic role
1990
T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis
Ota K, Matsui M, Milford E, Mackin G, Weiner H, Hafler D. T-cell recognition of an immuno-dominant myelin basic protein epitope in multiple sclerosis. Nature 1990, 346: 183-187. PMID: 1694970, DOI: 10.1038/346183a0.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAntigen-Presenting CellsApoproteinsAutoantigensCells, CulturedEpitopesHLA-DR AntigensHumansIn Vitro TechniquesMajor Histocompatibility ComplexMolecular Sequence DataMultiple SclerosisMyelin Basic ProteinMyelin ProteinsMyelin Proteolipid ProteinPeptide FragmentsT-LymphocytesConceptsMultiple sclerosis patientsT cell linesMyelin basic proteinMultiple sclerosisSclerosis patientsT cellsVivo-activated T cellsShort-term T cell linesMyelin basic protein epitopeBasic proteinExperimental autoimmune encephalomyelitisDifferent T-cell linesCentral nervous systemMultiple sclerosis subjectsT cell recognitionT cell specificityAutoimmune encephalomyelitisImmune involvementAutoimmune diseasesPotential autoantigensNormal controlsNervous systemNeurological diseasesSclerosisPatients
1989
Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid
Chofflon M, Weiner H, Morimoto C, Hafler D. Decrease of suppressor inducer (cd4+ 2h4+) t cells in multiple sclerosis cerebrospinal fluid. Annals Of Neurology 1989, 25: 494-499. PMID: 2528316, DOI: 10.1002/ana.410250512.Peer-Reviewed Original ResearchConceptsInducer T cellsSuppressor-inducer T cellsMultiple sclerosis patientsT cellsCerebrospinal fluidMultiple sclerosisPeripheral bloodSclerosis patientsInducer cellsInducer functionMultiple sclerosis cerebrospinal fluidHelper-inducer T cellsCentral nervous system compartmentHelper inducer functionHelper-inducer cellsLocal autoimmune processesSuppressor-inducer functionSuppressor-inducer cellsCentral nervous systemSamples of bloodFlow cytometric analysisHelper inducerAutoimmune processInflammatory disordersT lymphocytes
1987
T Cells in Multiple Sclerosis and Inflammatory Central Nervous System Diseases
Hafler D, Weiner H. T Cells in Multiple Sclerosis and Inflammatory Central Nervous System Diseases. Immunological Reviews 1987, 100: 307-332. PMID: 3326824, DOI: 10.1111/j.1600-065x.1987.tb00537.x.Peer-Reviewed Original ResearchConceptsT cellsInflammatory responseCNS tissueInflammatory central nervous system diseasesProgressive multiple sclerosis patientsCentral nervous system diseaseClass II MHC antigensMonoclonal antibodiesT-cell receptor gene rearrangementsCSF T cellsOngoing inflammatory responseTotal T cellsInflammatory CNS diseaseMultiple sclerosis patientsAnti-measles antibodiesAntigen-presenting cellsChronic disease processesAntigen-specific cellsNervous system diseasesReceptor gene rearrangementsMurine monoclonal antibodiesSelective accumulationAlpha beta chainsCNS damageSclerosis patientsImmunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies.
Dawson DM, Carter JL, Hafler DA, Weiner HL. Immunosuppression in progressive multiple sclerosis with high dose intravenous cyclophosphamide and monoclonal antibodies. Nuova Rivista Di Neurologia 1987, 57: 88-91. PMID: 3039645.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisMonoclonal antibody therapyMultiple sclerosisAntibody therapyChronic progressive multiple sclerosisHigh-dose intravenous cyclophosphamideMultiple sclerosis patientsForm of treatmentLong-term controlIntravenous cyclophosphamideSclerosis patientsClinical resultsSerious toxicityImmune parametersPilot trialCyclophosphamideNervous systemSclerosisTerm controlsPatientsMonoclonal antibodiesACTHOnly small numbersTherapyAdverse effects
1986
Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis
Johnson D, Hafler D, Fallis R, Lees M, Brady R, Quarles R, Weiner H. Cell-mediated immunity to myelin-associated glycoprotein, proteolipid protein, and myelin basic protein in multiple sclerosis. Journal Of Neuroimmunology 1986, 13: 99-108. PMID: 2428837, DOI: 10.1016/0165-5728(86)90053-6.Peer-Reviewed Original ResearchConceptsActive MS patientsMyelin basic proteinPeripheral blood lymphocytesMyelin antigensMS patientsControl subjectsActive MSMultiple sclerosisNeurologic diseaseProteolipid proteinStable multiple sclerosis patientsMean proliferative responseCell-mediated immunityMultiple sclerosis patientsBasic proteinStable MSOND groupSclerosis patientsT8 subsetsBlood lymphocytesLymphocyte stimulationProliferative responseProportion of individualsPatientsAntigenImmunologic responses of progressive multiple sclerosis patients treated with an anti-T-cell monoclonal antibody, anti-T12.
Hafler D, Fallis R, Dawson D, Schlossman S, Reinherz E, Weiner H. Immunologic responses of progressive multiple sclerosis patients treated with an anti-T-cell monoclonal antibody, anti-T12. Neurology 1986, 36: 777-84. PMID: 3486383, DOI: 10.1212/wnl.36.6.777.Peer-Reviewed Original ResearchConceptsHuman anti-mouse antibodiesAnti-mouse antibodiesDay 3Anti-T cell monoclonal antibodiesProgressive multiple sclerosis patientsPost-thymic T cellsMultiple sclerosis patientsMild allergic reactionsProgression of diseaseMonoclonal Antibodies ReactiveEffect of treatmentPhase one studyProgressive MSClinical effectsSclerosis patientsImmunologic responseBlood levelsImmunologic studiesPokeweed mitogenAllergic reactionsT cellsAntibody reactivePatientsDay 1Day 7
1985
Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases
Hafler DA, Hemler ME, Christenson L, Williams JM, Shapiro HM, Strom TB, Strominger JL, Weiner HL. Investigation of in vivo activated T cells in multiple sclerosis and inflammatory central nervous system diseases. Clinical Immunology 1985, 37: 163-171. PMID: 3930113, DOI: 10.1016/0090-1229(85)90147-3.Peer-Reviewed Original ResearchConceptsT cellsActivated T cellsActivation antigensMultiple sclerosisInflammatory central nervous system diseasesPeripheral blood T cellsCentral nervous system diseaseActive multiple sclerosisSystemic immune activationGroup of patientsMultiple sclerosis patientsBlood T cellsEarly activation antigenNervous system diseasesAbnormal immunologic activityMultiple differentiation stagesMS patientsSclerosis patientsViral encephalitisImmune activationPeripheral bloodNeurologic diseaseImmunologic activitySystem diseasesNormal controlsDecreased autologous mixed lymphocyte reaction in multiple sclerosis
Hafler D, Buchsbaum M, Weiner H. Decreased autologous mixed lymphocyte reaction in multiple sclerosis. Journal Of Neuroimmunology 1985, 9: 339-347. PMID: 2931449, DOI: 10.1016/s0165-5728(85)80034-5.Peer-Reviewed Original ResearchConceptsT4/T8 ratioHigh T4/T8 ratioT8 ratioMultiple sclerosisNormal controlsInactive patientsActive diseaseMS patientsAutologous mixed lymphocyte reactionActive MS patientsSubgroup of patientsT cell responsesT cell subsetsMultiple sclerosis patientsT4/T8Mixed lymphocyte reactionCentral nervous systemSclerosis patientsLymphocyte reactionAutoimmune diseasesT cellsPatientsNervous systemViral disordersAMLR