2024
Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains
Zhu B, Park J, Coffey S, Russo A, Hsu I, Wang J, Su C, Chang R, Lam T, Gopal P, Ginsberg S, Zhao H, Hafler D, Chandra S, Zhang L. Single-cell transcriptomic and proteomic analysis of Parkinson’s disease brains. Science Translational Medicine 2024, 16: eabo1997. PMID: 39475571, DOI: 10.1126/scitranslmed.abo1997.Peer-Reviewed Original ResearchConceptsProteomic analysisAlzheimer's diseasePrefrontal cortexBrain cell typesGenetics of PDParkinson's diseaseCell-cell interactionsChaperone expressionSingle-nucleus transcriptomesExpressed genesTranscriptional changesPostmortem human brainPostmortem brain tissueDiseased brainSynaptic proteinsSingle-cellDown-regulationBrain cell populationsBrain regionsCell typesNeurodegenerative disordersLate-stage PDParkinson's disease brainsDisease etiologyNeuronal vulnerabilitySingle-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE)
Hanin A, Zhang L, Huttner A, Plu I, Mathon B, Bielle F, Navarro V, Hirsch L, Hafler D. Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE). Neurology Neuroimmunology & Neuroinflammation 2024, 11: e200259. PMID: 38810181, PMCID: PMC11139018, DOI: 10.1212/nxi.0000000000200259.Peer-Reviewed Original ResearchConceptsNew-onset refractory status epilepticusTemporal lobe epilepsyGABAergic neuronsExcitatory neuronsInfiltrating macrophagesProportion of GABAergic neuronsChronic temporal lobe epilepsyRefractory status epilepticusInhibitory GABAergic neuronsSingle-cell transcriptome analysisDecreased expression of genesDegree of demyelinationImmune disturbancesNeuronal excitabilityImmune dysregulationNew-onsetStatus epilepticusPoor outcomeRefractory epilepsyHealthy childrenMicroglial reactivitySingle-nucleus RNA sequencingNLRP3 inflammasome activationInflammatory responseLobe epilepsy
2022
Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain
Marsh SE, Walker AJ, Kamath T, Dissing-Olesen L, Hammond TR, de Soysa TY, Young AMH, Murphy S, Abdulraouf A, Nadaf N, Dufort C, Walker AC, Lucca LE, Kozareva V, Vanderburg C, Hong S, Bulstrode H, Hutchinson PJ, Gaffney DJ, Hafler DA, Franklin RJM, Macosko EZ, Stevens B. Dissection of artifactual and confounding glial signatures by single-cell sequencing of mouse and human brain. Nature Neuroscience 2022, 25: 306-316. PMID: 35260865, DOI: 10.1038/s41593-022-01022-8.Peer-Reviewed Original ResearchConceptsSingle-cell sequencing experimentsCell type diversitySingle-cell sequencingRNA-sequencing datasetsGene expression changesGene expression signaturesVivo gene expressionTranscriptional profilesGene expressionExpression changesSequencing experimentsGlial signaturesDownstream analysisExpression signaturesTissue typesSingle cell suspensionsOptimal cell yieldIntact tissueHuman tissuesCell yieldEnzymatic dissociationHuman samplesTissue digestionPostmortem human samplesTissue
2019
Multiple sclerosis enters a grey area
Pappalardo JL, Hafler DA. Multiple sclerosis enters a grey area. Nature 2019, 566: 465-466. PMID: 30809050, DOI: 10.1038/d41586-019-00563-6.Peer-Reviewed Original Research
2016
Power estimation for non-standardized multisite studies
Keshavan A, Paul F, Beyer MK, Zhu AH, Papinutto N, Shinohara RT, Stern W, Amann M, Bakshi R, Bischof A, Carriero A, Comabella M, Crane JC, D'Alfonso S, Demaerel P, Dubois B, Filippi M, Fleischer V, Fontaine B, Gaetano L, Goris A, Graetz C, Gröger A, Groppa S, Hafler DA, Harbo HF, Hemmer B, Jordan K, Kappos L, Kirkish G, Llufriu S, Magon S, Martinelli-Boneschi F, McCauley JL, Montalban X, Mühlau M, Pelletier D, Pattany PM, Pericak-Vance M, Cournu-Rebeix I, Rocca MA, Rovira A, Schlaeger R, Saiz A, Sprenger T, Stecco A, Uitdehaag BMJ, Villoslada P, Wattjes MP, Weiner H, Wuerfel J, Zimmer C, Zipp F, Consortium I, Hauser SL, Oksenberg JR, Henry RG. Power estimation for non-standardized multisite studies. NeuroImage 2016, 134: 281-294. PMID: 27039700, PMCID: PMC5656257, DOI: 10.1016/j.neuroimage.2016.03.051.Peer-Reviewed Original Research
2015
Biomarkers in multiple sclerosis
Housley WJ, Pitt D, Hafler DA. Biomarkers in multiple sclerosis. Clinical Immunology 2015, 161: 51-58. PMID: 26143623, DOI: 10.1016/j.clim.2015.06.015.Peer-Reviewed Original ResearchConceptsMultiple sclerosisB cell chemoattractant CXCL13Myelin-reactive T cellsMacrophage marker CD163Reactive T cellsMarkers of neurodegenerationKIR4.1 antibodiesMS seraClinical outcomesOligoclonal bandsYKL-40Disease progressionT cellsMS susceptibilityCerebrospinal fluidPotential biomarkersViral titersClinical useBiomarkersBiomarker researchSclerosisProgressionDisease diagnosisCD163CXCL13
2014
B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes
Stern JN, Yaari G, Vander Heiden JA, Church G, Donahue WF, Hintzen RQ, Huttner AJ, Laman JD, Nagra RM, Nylander A, Pitt D, Ramanan S, Siddiqui BA, Vigneault F, Kleinstein SH, Hafler DA, O'Connor KC. B cells populating the multiple sclerosis brain mature in the draining cervical lymph nodes. Science Translational Medicine 2014, 6: 248ra107. PMID: 25100741, PMCID: PMC4388137, DOI: 10.1126/scitranslmed.3008879.Peer-Reviewed Original ResearchConceptsCervical lymph nodesCentral nervous systemB cellsCerebrospinal fluidLymph nodesMultiple sclerosisLymphoid tissueCNS of patientsCNS B cellsAntigen-experienced B cellsMultiple sclerosis brainSecondary lymphoid tissuesB cell compartmentB cell trafficB cell maturationImmunomodulatory therapyImmune infiltratesPeripheral bloodInflammatory diseasesLymphocyte transmigrationPeripheral tissuesNervous systemMembers of clonesCell maturationCell traffic
2009
Epstein–Barr virus infection is not a characteristic feature of multiple sclerosis brain
Willis SN, Stadelmann C, Rodig SJ, Caron T, Gattenloehner S, Mallozzi SS, Roughan JE, Almendinger SE, Blewett MM, Brück W, Hafler DA, O’Connor K. Epstein–Barr virus infection is not a characteristic feature of multiple sclerosis brain. Brain 2009, 132: 3318-3328. PMID: 19638446, PMCID: PMC2792367, DOI: 10.1093/brain/awp200.Peer-Reviewed Original ResearchConceptsMultiple sclerosis brainEpstein-Barr virus infectionEBV infectionWhite matter lesionsMultiple sclerosisCentral nervous systemMatter lesionsVirus infectionSecond cohortEBV infected cellsB cell infiltrationB cell aggregatesInflammatory demyelinating diseaseB-cell infiltratesReal-time polymerase chain reaction methodologyCNS immunopathologyCNS lymphomaDemyelinating diseaseCell infiltrateSitu hybridizationCell infiltrationLarge cohortBrain pathologyNervous systemPolymerase chain reaction methodology
2008
CTLA4Ig treatment in patients with multiple sclerosis
Viglietta V, Bourcier K, Buckle GJ, Healy B, Weiner HL, Hafler DA, Egorova S, Guttmann CR, Rusche JR, Khoury SJ. CTLA4Ig treatment in patients with multiple sclerosis. Neurology 2008, 71: 917-924. PMID: 18794494, DOI: 10.1212/01.wnl.0000325915.00112.61.Peer-Reviewed Original ResearchConceptsMultiple sclerosisCostimulatory pathwayPhase 1 dose-escalation studyT cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseRelapsing-remitting multiple sclerosisT-cell costimulatory pathwaysCostimulatory molecule interactionsMonths of infusionDose-escalation studyInterferon-gamma productionT cell activationOriginal therapeutic approachAdverse eventsImmunologic assessmentImmunologic effectsCTLA4Ig treatmentChronic inflammationAutoimmune diseasesInflammatory processT cellsImmune responseTherapeutic approachesCTLA4IgExtension study
2000
Ubiquitous pathogens: links between infection and autoimmunity in MS?
Hunter S, Hafler D. Ubiquitous pathogens: links between infection and autoimmunity in MS? Neurology 2000, 55: 164-5. PMID: 10908883, DOI: 10.1212/wnl.55.2.164.Peer-Reviewed Original Research
1997
Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity
Dangond F, Windhagen A, Groves C, Hafler D. Constitutive expression of costimulatory molecules by human microglia and its relevance to CNS autoimmunity. Journal Of Neuroimmunology 1997, 76: 132-138. PMID: 9184642, DOI: 10.1016/s0165-5728(97)00043-x.Peer-Reviewed Original ResearchConceptsCentral nervous systemCostimulatory moleculesHuman microgliaMyelin-reactive T cellsTh1 T cell responsesExpression of B7.1Reactive T cellsT cell responsesMultiple sclerosis plaquesT cell surface moleculesB7.2 costimulatory moleculesMHC-antigen complexesT cell activationT cell receptorCNS autoimmunityCNS inflammationB7.2 expressionBiopsy specimensB7 familyT cellsNormal brainMicrogliaNervous systemB7.1High expression
1995
Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions.
Windhagen A, Newcombe J, Dangond F, Strand C, Woodroofe MN, Cuzner ML, Hafler DA. Expression of costimulatory molecules B7-1 (CD80), B7-2 (CD86), and interleukin 12 cytokine in multiple sclerosis lesions. Journal Of Experimental Medicine 1995, 182: 1985-1996. PMID: 7500044, PMCID: PMC2192240, DOI: 10.1084/jem.182.6.1985.Peer-Reviewed Original ResearchConceptsAutoreactive T cellsMultiple sclerosisT cellsB7-1Autoimmune diseasesCostimulatory moleculesMS plaquesB7-2T cell-mediated autoimmune diseaseInitiation of MSMyelin-autoreactive T cellsCell-mediated autoimmune diseaseSelf-reactive T cellsCostimulatory molecules B7-1Acute MS plaquesAutoimmune animal modelsInterleukin-12 cytokinesPutative autoimmune diseaseSemiquantitative reverse transcriptase-polymerase chain reactionReverse transcriptase-polymerase chain reactionExpression of cytokinesTranscriptase-polymerase chain reactionT cell activationMultiple sclerosis lesionsInflammatory cuffsCase 37-1995 — A 6-year-old boy with a rash, meningismus, and diplegia
Cabot R, Scully R, Mark E, McNeely W, McNeely B, Hafler D, Hedley-Whyte E. Case 37-1995 — A 6-year-old boy with a rash, meningismus, and diplegia. New England Journal Of Medicine 1995, 333: 1485-1493. PMID: 7477150, DOI: 10.1056/nejm199511303332208.Peer-Reviewed Original ResearchReactivity 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 cells
1988
Immunohistochemical Analysis of Suppressor‐Inducer and Helper‐Inducer T Cells in Multiple Sclerosis Brain Tissue
SOBEL R, HAFLER D, CASTRO E, MORIMOTO C, WEINER H. Immunohistochemical Analysis of Suppressor‐Inducer and Helper‐Inducer T Cells in Multiple Sclerosis Brain Tissue. Annals Of The New York Academy Of Sciences 1988, 540: 306-308. PMID: 2905121, DOI: 10.1111/j.1749-6632.1988.tb27082.x.Peer-Reviewed Original ResearchThe 2H4 (CD45R) antigen is selectively decreased in multiple sclerosis lesions.
Sobel RA, Hafler DA, Castro EE, Morimoto C, Weiner HL. The 2H4 (CD45R) antigen is selectively decreased in multiple sclerosis lesions. The Journal Of Immunology 1988, 140: 2210-4. PMID: 2965183, DOI: 10.4049/jimmunol.140.7.2210.Peer-Reviewed Original ResearchConceptsMultiple sclerosisViral encephalitisImmune responseCentral nervous system immune responseSuppressor-inducer functionCentral nervous system tissuePlaque edgeAdjacent white matterIL-2R mAbNervous system tissueMultiple sclerosis lesionsAnti-2H4Anti-CD4Inflammatory cellsMS plaquesImmunohistochemical stainingWhite matterSclerosis lesionsEncephalitisPatientsCellsRare cellsCD8CD4Sclerosis
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
1985
Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis
Hafler D, Buchsbaum M, Johnson D, Weiner H. Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis. Annals Of Neurology 1985, 18: 451-458. PMID: 2416267, DOI: 10.1002/ana.410180407.Peer-Reviewed Original ResearchConceptsMultiple sclerosisBlood of patientsT cellsMyelin basic proteinCerebrospinal fluid lymphocytesT-cell abnormalitiesCSF of patientsAntigen-specific cellsIndividual T cellsBasic proteinSuppressor cellsViral meningoencephalitisStimulating lymphocytesInterleukin-2Antigen reactivityCell abnormalitiesCerebrospinal fluidSingle cell clonal analysisPatientsT8 populationWhite matterBloodCSFSclerosisLymphocytes
1984
T Cell Subsets in Patients with Multiple Sclerosis: An Overviewa
WEINER H, HAFLER D, FALLIS R, JOHNSON D, AULT K, HAUSER S. T Cell Subsets in Patients with Multiple Sclerosis: An Overviewa. Annals Of The New York Academy Of Sciences 1984, 436: 281-290. PMID: 6152384, DOI: 10.1111/j.1749-6632.1984.tb14800.x.Peer-Reviewed Original Research