2022
The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome
Longbrake EE, Hua LH, Mowry EM, Gauthier SA, Alvarez E, Cross AH, Pei J, Priest J, Raposo C, Hafler DA, Winger RC. The CELLO trial: Protocol of a planned phase 4 study to assess the efficacy of Ocrelizumab in patients with radiologically isolated syndrome. Multiple Sclerosis And Related Disorders 2022, 68: 104143. PMID: 36031693, PMCID: PMC9772048, DOI: 10.1016/j.msard.2022.104143.Peer-Reviewed Original ResearchConceptsEfficacy of ocrelizumabMultiple sclerosisImmunologic biomarkersClinical trialsTransient B-cell depletionClinical multiple sclerosisCSF immune cellsEffects of ocrelizumabMS disease pathophysiologyNew brain lesionsOvert neurological symptomsB-cell depletionPlacebo-controlled studyPhase 4 studyLong-term outcomesPatient-reported outcomesPrimary progressive MSHumanized monoclonal antibodyFirst-degree relativesB cell biologySubtle cognitive impairmentEligible patientsImmune recoveryProgressive MSWeek 48
2016
CNS demyelination and enhanced myelin-reactive responses after ipilimumab treatment
Cao Y, Nylander A, Ramanan S, Goods BA, Ponath G, Zabad R, Chiang VL, Vortmeyer AO, Hafler DA, Pitt D. CNS demyelination and enhanced myelin-reactive responses after ipilimumab treatment. Neurology 2016, 86: 1553-1556. PMID: 26984943, PMCID: PMC5573201, DOI: 10.1212/wnl.0000000000002594.Peer-Reviewed Original Research
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
2008
Cytometric profiling in multiple sclerosis uncovers patient population structure and a reduction of CD8low cells
De Jager PL, Rossin E, Pyne S, Tamayo P, Ottoboni L, Viglietta V, Weiner M, Soler D, Izmailova E, Faron-Yowe L, O’Brien C, Freeman S, Granados S, Parker A, Roubenoff R, Mesirov JP, Khoury SJ, Hafler DA, Weiner HL. Cytometric profiling in multiple sclerosis uncovers patient population structure and a reduction of CD8low cells. Brain 2008, 131: 1701-1711. PMID: 18567923, PMCID: PMC2730047, DOI: 10.1093/brain/awn118.Peer-Reviewed Original ResearchConceptsRelapsing-remitting MSImmunological profileRRMS subjectsPeripheral bloodUntreated subjectsNatural killer cell profileComprehensive Longitudinal InvestigationAbsence of treatmentCell surface markersCIS subjectsDemyelinating diseaseDemyelination syndromeWomen's HospitalHealthy controlsCytometric profilingCell profilesMonoclonal antibodiesExtension phaseFresh bloodBiomarker discovery effortsDistinct subsetsBloodCell populationsGating strategyHospital
1999
The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis
Hafler DA. The distinction blurs between an autoimmune versus microbial hypothesis in multiple sclerosis. Journal Of Clinical Investigation 1999, 104: 527-529. PMID: 10487765, PMCID: PMC483283, DOI: 10.1172/jci8193.Peer-Reviewed Original ResearchAnimalsAntigen PresentationAntigens, ViralAutoantigensAutoimmune DiseasesCardiovirus InfectionsCross ReactionsDemyelinating DiseasesDisease Models, AnimalDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalEpitopesHuman T-lymphotropic virus 1HumansMiceMicrogliaModels, ImmunologicalMolecular MimicryMultiple SclerosisMyelin ProteinsParaparesis, Tropical SpasticT-Lymphocyte SubsetsTheilovirusVirus Diseases
1998
Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis
Pohl-Koppe A, Burchett S, Thiele E, Hafler D. Myelin basic protein reactive Th2 T cells are found in acute disseminated encephalomyelitis. Journal Of Neuroimmunology 1998, 91: 19-27. PMID: 9846815, DOI: 10.1016/s0165-5728(98)00125-8.Peer-Reviewed Original ResearchMeSH KeywordsAntibodies, ViralAutoimmunityChildChild, PreschoolDemyelinating DiseasesEncephalomyelitis, Acute DisseminatedEncephalomyelitis, Autoimmune, ExperimentalEpitopesFemaleHerpes ZosterHerpesvirus 3, HumanHumansInfantInterferon-gammaInterleukin-2Interleukin-4MaleMyelin Basic ProteinT-LymphocytesConceptsAcute disseminated encephalomyelitisMBP-reactive T cell linesCentral nervous systemT cellsIL-4T cell linesDisseminated encephalomyelitisSignificant IFN-gamma secretionMyelin-reactive T cellsIFN-gamma secretionIL-4 secretionTh2 T cellsCell linesAutoimmune diseasesPredominant cytokineNormal subjectsSpontaneous recoveryNervous systemPatientsEncephalomyelitisCytokinesSecretionRecovery phaseCellsSubjects
1996
TCR usage in human and experimental demyelinating disease
Hafler D, Saadeh M, Kuchroo V, Milford E, Steinman L. TCR usage in human and experimental demyelinating disease. Trends In Immunology 1996, 17: 152-159. PMID: 8871344, DOI: 10.1016/0167-5699(96)80611-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConserved SequenceDemyelinating DiseasesEncephalomyelitis, Autoimmune, ExperimentalHumansMultiple SclerosisReceptors, Antigen, T-Cell, alpha-beta
1991
Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig
Brod S, al‐Sabbagh A, Sobel R, Hafler D, Weiner H. Suppression of experimental autoimmune encephalomyelitis by oral administration of myelin antigens: IV. Suppression of chronic relapsing disease in the lewis rat and strain 13 guinea pig. Annals Of Neurology 1991, 29: 615-622. PMID: 1716432, DOI: 10.1002/ana.410290608.Peer-Reviewed Original ResearchConceptsExperimental autoimmune encephalomyelitisAutoimmune encephalomyelitisMyelin antigensGuinea pig myelinOral administrationCentral nervous systemLewis ratsMyelin basic proteinAntigen-specific peripheral immune toleranceGuinea pigsMonophasic experimental autoimmune encephalomyelitisDelayed-type hypersensitivity responseGuinea pig myelin basic proteinHuman demyelinating disordersOngoing immune responsePig myelin basic proteinComplete Freund's adjuvantPeripheral immune toleranceExacerbation of diseaseHuman autoimmune diseasesBasic proteinClinical relapseDemyelinating disorderOral toleranceCNS demyelination