2015
Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis
Cao Y, Goods BA, Raddassi K, Nepom GT, Kwok WW, Love JC, Hafler DA. Functional inflammatory profiles distinguish myelin-reactive T cells from patients with multiple sclerosis. Science Translational Medicine 2015, 7: 287ra74. PMID: 25972006, PMCID: PMC4497538, DOI: 10.1126/scitranslmed.aaa8038.Peer-Reviewed Original ResearchConceptsMyelin-reactive T cellsMultiple sclerosisT cellsHealthy controlsT cell librariesT helper cell 17Antigen-specific T cellsGene signatureMore IL-10More proinflammatory cytokinesAutoreactive T cellsIL-10 productionHuman autoimmune diseasesGranulocyte-macrophage colony-stimulating factorProduction of interferonColony-stimulating factorMyelin antigensTh17 cellsIL-10Inflammatory profileInterleukin-17Proinflammatory cytokinesAutoimmune diseasesDisease progressionHealthy subjects
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
Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid
Owens GP, Bennett JL, Lassmann H, O'Connor KC, Ritchie AM, Shearer A, Lam C, Yu X, Birlea M, DuPree C, Williamson RA, Hafler DA, Burgoon MP, Gilden D. Antibodies produced by clonally expanded plasma cells in multiple sclerosis cerebrospinal fluid. Annals Of Neurology 2009, 65: 639-649. PMID: 19557869, PMCID: PMC2843543, DOI: 10.1002/ana.21641.Peer-Reviewed Original ResearchConceptsMS cerebrospinal fluidMyelin oligodendrocyte glycoproteinMultiple sclerosisCerebrospinal fluidMyelin basic proteinMyelin antigensOligodendrocyte glycoproteinMultiple sclerosis cerebrospinal fluidOligoclonal B cell responseB cell clonal expansionIntrathecal IgG synthesisB cell responsesPlasma cell cloneB lymphocyte clonesHuman brain tissue sectionsTissue sectionsProteolipid proteinIndividual myelin proteinsBasic proteinBrain tissue sectionsIgG synthesisInflammatory cellsHumoral responseControl brainsPlasma cells
2003
In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis
Schmied M, Duda PW, Krieger JI, Trollmo C, Hafler DA. In vitro evidence that subcutaneous administration of glatiramer acetate induces hyporesponsive T cells in patients with multiple sclerosis. Clinical Immunology 2003, 106: 163-174. PMID: 12706402, DOI: 10.1016/s1521-6616(03)00020-2.Peer-Reviewed Original ResearchConceptsGA-reactive T cellsT cell reactivityT cellsRR-MSMultiple sclerosisCell reactivityT cell peripheral toleranceTh2-type T cellsT cell frequenciesMonths of treatmentT cell hyporesponsivenessT cell populationsT cell nonresponsivenessT cell anergyHyporesponsive T cellsMechanism of actionMyelin antigensGlatiramer acetatePeripheral toleranceCell hyporesponsivenessPeripheral bloodClonal eliminationIL-2Cell anergySubcutaneous administration
1999
Cross-Reactivity of Borrelia burgdorferi and Myelin Basic Protein-Specific T Cells Is Not Observed in Borrelial Encephalomyelitis
Pohl-Koppe A, Logigian E, Steere A, Hafler D. Cross-Reactivity of Borrelia burgdorferi and Myelin Basic Protein-Specific T Cells Is Not Observed in Borrelial Encephalomyelitis. Cellular Immunology 1999, 194: 118-123. PMID: 10357888, DOI: 10.1006/cimm.1999.1495.Peer-Reviewed Original ResearchConceptsMyelin basic proteinT cell linesB. burgdorferiMyelin basic protein-specific T cellsT cell autoimmune responsesShort-term T cell linesLate Lyme diseaseT cell responsesT cell clonesWhite matter diseaseMyelin antigensTransverse myelitisRare manifestationAutoimmune responseMultiple sclerosisPathogenetic roleHealthy controlsT cellsLike diseaseWhite matterPatientsEncephalomyelitisLyme borreliosisLyme diseaseBorrelia burgdorferi
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
1996
Three‐year Open Protocol Continuation Study of Oral Tolerization with Myelin Antigens in Multiple Sclerosis and Design of a Phase III Pivotal Trial
HOHOL M, KHOURY S, COOK S, ORAV E, HAFLER D, WEINER H. Three‐year Open Protocol Continuation Study of Oral Tolerization with Myelin Antigens in Multiple Sclerosis and Design of a Phase III Pivotal Trial. Annals Of The New York Academy Of Sciences 1996, 778: 243-250. PMID: 8610977, DOI: 10.1111/j.1749-6632.1996.tb21132.x.Peer-Reviewed Original Research
1995
A Review of T‐Cell Receptors in Multiple Sclerosis: Clonal Expansion and Persistence of Human T‐Cells Specific for an Immunodominant Myelin Basic Protein Peptidea
WUCHERPFENNIG K, HAFLER D. A Review of T‐Cell Receptors in Multiple Sclerosis: Clonal Expansion and Persistence of Human T‐Cells Specific for an Immunodominant Myelin Basic Protein Peptidea. Annals Of The New York Academy Of Sciences 1995, 756: 241-258. PMID: 7544075, DOI: 10.1111/j.1749-6632.1995.tb44522.x.Peer-Reviewed Original ResearchConceptsImmunodominant MBP peptidesT cell clonesMBP peptidesImmune responseNormal subjectsMBP-specific T cell clonesIndividual multiple sclerosis patientsTCR beta-chain usageMBP-specific T cellsTCR V beta chainsDR2 haplotypeSpecific T cell clonesBeta-chain usageT cell responsesAntigen-specific therapyMultiple sclerosis patientsSpecific T cellsDifferent T-cell linesT Cells SpecificIdentical TCR sequencesT cell receptorT cell linesAlpha-chain rearrangementMyelin antigensMS patients
1993
Double-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis
Weiner H, Mackin G, Matsui M, Orav E, Khoury S, Dawson D, Hafler D. Double-Blind Pilot Trial of Oral Tolerization with Myelin Antigens in Multiple Sclerosis. Science 1993, 259: 1321-1324. PMID: 7680493, DOI: 10.1126/science.7680493.Peer-Reviewed Original ResearchConceptsMultiple sclerosisOral tolerizationMyelin antigensAutoimmune diseasesDouble-blind pilot trialRelapsing-remitting multiple sclerosisDouble-blind studyCentral nervous systemMyelin basic proteinMajor exacerbationsDaily capsuleT cellsT lymphocytesPilot trialSide effectsNervous systemControl groupMyelin componentsBovine myelinDiseaseMyelinTolerizationSclerosisAntigenBasic protein
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
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 individualsPatientsAntigen