2014
Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells
Lee MN, Ye C, Villani AC, Raj T, Li W, Eisenhaure TM, Imboywa SH, Chipendo PI, Ran FA, Slowikowski K, Ward LD, Raddassi K, McCabe C, Lee MH, Frohlich IY, Hafler DA, Kellis M, Raychaudhuri S, Zhang F, Stranger BE, Benoist CO, De Jager PL, Regev A, Hacohen N. Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells. Science 2014, 343: 1246980. PMID: 24604203, PMCID: PMC4124741, DOI: 10.1126/science.1246980.Peer-Reviewed Original ResearchMeSH KeywordsAdultAutoimmune DiseasesCommunicable DiseasesDendritic CellsEscherichia coliFemaleGene-Environment InteractionGenetic LociGenome-Wide Association StudyHEK293 CellsHost-Pathogen InteractionsHumansInfluenza A virusInterferon Regulatory Factor-7Interferon-betaLipopolysaccharidesMaleMiddle AgedPolymorphism, Single NucleotideQuantitative Trait LociSTAT Transcription FactorsTranscriptomeYoung AdultConceptsGenetic variationPathogen-responsive genesHuman genetic variationGenetic variantsIRF transcription factorsCommon genetic variantsType I IFN inductionFunctional annotationExpression responsesTranscription factorsI IFN inductionCausal variantsPathogen sensingEnvironmental stimuliComplex diseasesCommon variantsCommon allelesIFN inductionComputational approachVariantsCellsInductionGenesInterindividual variationSTAT
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
2011
Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease
Dominguez-Villar M, Baecher-Allan CM, Hafler DA. Identification of T helper type 1–like, Foxp3+ regulatory T cells in human autoimmune disease. Nature Medicine 2011, 17: 673-675. PMID: 21540856, PMCID: PMC3675886, DOI: 10.1038/nm.2389.Peer-Reviewed Original ResearchConceptsTreg cellsT helper type 1Regulatory T cellsT regulatory (Treg) cellsHelper type 1T helper typeHuman autoimmune diseasesHuman Treg cellsRegulatory cellsIL-12Multiple sclerosisAutoimmune diseasesPeripheral bloodHelper typeT cellsSuppressive activityType 1Functional plasticityConsiderable phenotypicCellsSclerosisIFNDiseaseMiceBloodInterferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonβ therapy in multiple sclerosis
Vosslamber S, van der Voort LF, van den Elskamp IJ, Heijmans R, Aubin C, Uitdehaag BM, Crusius JB, van der PouwKraan T, Comabella M, Montalban X, Hafler DA, De Jager PL, Killestein J, Polman CH, Verweij CL. Interferon regulatory factor 5 gene variants and pharmacological and clinical outcome of Interferonβ therapy in multiple sclerosis. Genes & Immunity 2011, 12: 466-472. PMID: 21471993, DOI: 10.1038/gene.2011.18.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisNon-responder statusInterferon regulatory factor 5IFNβ treatmentMultiple sclerosisT2 lesionsClinical outcomesMore magnetic resonance imagingMore T2 lesionsStart of therapyGene variantsInterferon-β TherapyIFN response genesRegulatory factor 5Poor pharmacological responseMagnetic resonance imagingIFNβ therapyClinical responseFirst relapseIndependent cohortPharmacological responseClinical relevanceG allelePatientsResonance imaging
2010
Population structure and HLA DRB1*1501 in the response of subjects with multiple sclerosis to first-line treatments
Gross R, Healy BC, Cepok S, Chitnis T, Khoury SJ, Hemmer B, Weiner HL, Hafler DA, De Jager PL. Population structure and HLA DRB1*1501 in the response of subjects with multiple sclerosis to first-line treatments. Journal Of Neuroimmunology 2010, 233: 168-174. PMID: 21115201, DOI: 10.1016/j.jneuroim.2010.10.038.Peer-Reviewed Original Research
1999
HTLV-I-Infected T Cells Evade the Antiproliferative Action of IFN-β
Smith D, Buckle G, Hafler D, Frank D, Höllsberg P. HTLV-I-Infected T Cells Evade the Antiproliferative Action of IFN-β. Virology 1999, 257: 314-321. PMID: 10329542, DOI: 10.1006/viro.1999.9679.Peer-Reviewed Original ResearchConceptsT cell clonesIFN-betaT cellsAntiproliferative actionHuman T-cell lymphotropic virus type IMyelopathy/tropical spastic paraparesisLymphotropic virus type INormal immunoregulatory mechanismsInnate immune defense mechanismsHost T cellsExogenous IL-2Tropical spastic paraparesisT cell proliferationImmune defense mechanismsVirus type IT cell activationPathogenesis of HTLVImmunoregulatory mechanismsSpastic paraparesisIL-2Phosphorylation of STAT1IFN-gammaViral infectionHigh dosesHTLV
1997
Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia
Smith D, Balashov K, Hafler D, Khoury S, Weiner H. Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia. Annals Of Neurology 1997, 42: 313-318. PMID: 9307252, DOI: 10.1002/ana.410420307.Peer-Reviewed Original ResearchConceptsMonthly intravenous methylprednisolonePulse cyclophosphamide therapyMultiple sclerosisImmune deviationIL-4Cyclophosphamide therapyIFN-beta1bMS patientsHealthy controlsTh1-type cell-mediated autoimmune diseaseCell-mediated autoimmune diseaseMethotrexate-treated patientsT-cell interferonUntreated MS patientsUntreated multiple sclerosisPeripheral blood eosinophiliaProgressive MS patientsTh2-type responseCyclophosphamide-treated patientsIL-10 productionInterleukin-4 productionMinimal IL-4Intravenous cyclophosphamideIntravenous methylprednisoloneBlood eosinophilia