2013
Serum 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 MSAutoantibodies
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
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 tissues
2001
In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG
Ohashi T, Yukitake M, Slavin A, Krieger J, Hafler D. In vitro evidence that immunuaffinity-purified MOG contains immunogenic quantities of contaminating mouse IgG; techniques for producing Ig-free MOG. Journal Of Neuroimmunology 2001, 118: 194-202. PMID: 11498254, DOI: 10.1016/s0165-5728(01)00321-6.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalAntibody SpecificityBlotting, WesternCell LineClone CellsCytokinesElectrophoresis, Polyacrylamide GelEnzyme-Linked Immunosorbent AssayFlow CytometryHumansImmunoglobulin GImmunophenotypingImmunosorbent TechniquesLymphocyte ActivationMiceMultiple SclerosisMyelin ProteinsMyelin SheathMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinSensitivity and SpecificityT-Lymphocytes
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 SpasticTheilovirusT-Lymphocyte SubsetsVirus Diseases
1996
Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients.
Fukaura H, Kent SC, Pietrusewicz MJ, Khoury SJ, Weiner HL, Hafler DA. Induction of circulating myelin basic protein and proteolipid protein-specific transforming growth factor-beta1-secreting Th3 T cells by oral administration of myelin in multiple sclerosis patients. Journal Of Clinical Investigation 1996, 98: 70-77. PMID: 8690806, PMCID: PMC507402, DOI: 10.1172/jci118779.Peer-Reviewed Original ResearchConceptsMyelin basic proteinT cellsOral administrationAutoimmune diseasesTetanus toxoidT cell linesMS patientsMultiple sclerosisProteolipid proteinFrequency of MBPNon-treated MS patientsPLP-reactive T cellsTh1-type autoimmune diseaseShort-term T cell linesCell-mediated autoimmune diseaseRelapsing-remitting MS patientsOriginal T cell cloneSpecific IFN-gammaSystemic immune toleranceExperimental autoimmune diseasesRegulatory T cellsReactive T cellsIFN-gamma secretionMultiple sclerosis patientsT cell clones
1995
T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans.
Markovic-Plese S, Fukaura H, Zhang J, al-Sabbagh A, Southwood S, Sette A, Kuchroo VK, Hafler DA. T cell recognition of immunodominant and cryptic proteolipid protein epitopes in humans. The Journal Of Immunology 1995, 155: 982-92. PMID: 7541828, DOI: 10.4049/jimmunol.155.2.982.Peer-Reviewed Original ResearchConceptsMultiple sclerosisT cellsPLP epitopesMHC class II isotypesPLP-reactive T cellsShort-term T cell linesCryptic epitopesProteolipid proteinT cell responsesT cell recognitionClass II isotypesT cell linesIndividual synthetic peptidesControl subjectsMHC restrictionImmune responseDR2 moleculesProliferative responseImmunodominant epitopesPLP peptidesProtein AgCell responsesCentral nervous system myelin proteinsMyelin proteinsEpitopes
1994
Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune Encephalomyelitis
Chen Y, Kuchroo V, Inobe J, Hafler D, Weiner H. Regulatory T Cell Clones Induced by Oral Tolerance: Suppression of Autoimmune Encephalomyelitis. Science 1994, 265: 1237-1240. PMID: 7520605, DOI: 10.1126/science.7520605.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, OralAmino Acid SequenceAnimalsCD4-Positive T-LymphocytesClone CellsEncephalomyelitis, Autoimmune, ExperimentalEpitopesImmune ToleranceInterleukin-10Interleukin-4Lymph NodesMajor Histocompatibility ComplexMesenteryMiceMolecular Sequence DataMyelin Basic ProteinMyelin ProteinsMyelin Proteolipid ProteinReceptors, Antigen, T-CellTransforming Growth Factor betaConceptsExperimental autoimmune encephalomyelitisMyelin basic proteinT cell clonesAutoimmune encephalomyelitisT cell receptor usageCell-mediated autoimmune diseaseMajor histocompatibility complex restrictionRegulatory T-cell clonesCell clonesMesenteric lymph nodesTh2-like clonesOral antigenOral toleranceEncephalitogenic CD4Lymph nodesPeripheral toleranceInterleukin-10Multiple sclerosisSJL miceAutoimmune diseasesOral administrationT cellsImmune responseInterleukin-4Animal modelsIncreased 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
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
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
1987
Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis.
Hafler DA, Benjamin DS, Burks J, Weiner HL. Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis. The Journal Of Immunology 1987, 139: 68-72. PMID: 2438352, DOI: 10.4049/jimmunol.139.1.68.Peer-Reviewed Original ResearchConceptsT cell clonesMyelin basic proteinPeripheral bloodPostinfectious encephalomyelitisCell clonesMultiple sclerosisT cellsProteolipid proteinPeripheral blood T cell clonesBlood T-cell clonePlaque tissueMS plaque tissueProportion of T4T cell reactivityHuman myelin basic proteinBasic proteinMS patientsCell reactivityIL-2Cerebrospinal fluidTarget antigenClear reactivityBrain tissueBloodEncephalomyelitis
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 individualsPatientsAntigenMonoclonal gammopathy and neuropathy: myelin-associated glycoprotein reactivity and clinical characteristics.
Hafler D, Johnson D, Kelly J, Panitch H, Kyle R, Weiner H. Monoclonal gammopathy and neuropathy: myelin-associated glycoprotein reactivity and clinical characteristics. Neurology 1986, 36: 75-8. PMID: 2417161, DOI: 10.1212/wnl.36.1.75.Peer-Reviewed Original ResearchConceptsMonoclonal gammopathySevere sensory-motor neuropathyAnti-MAG reactivityDistinct clinical entitySensory-motor neuropathyIgM monoclonal gammopathyClinical characteristicsMotor neuropathySensory neuropathyClinical entityGlycoprotein reactivityPatientsGammopathyNeuropathyImmunoblot analysisMyelinPolyneuropathySerum