2022
Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis
Asashima H, Axisa PP, Pham THG, Longbrake EE, Ruff WE, Lele N, Cohen I, Raddassi K, Sumida TS, Hafler DA. Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis. Journal Of Clinical Investigation 2022, 132: e156254. PMID: 36250467, PMCID: PMC9566906, DOI: 10.1172/jci156254.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisMemory B cellsCTfh cellsB cellsTIGIT expressionMultiple sclerosisT cellsFollicular helper T cellsHealthy age-matched controlsB-cell depletionT cell expansionHelper T cellsAge-matched controlsB cell functionB-cell pathwayDifferential gene expression signaturesTfh cellsDisease activityGene expression signaturesCell depletionCD40 ligandTranscription factor TCF4Disease pathogenesisImmune systemNew MRI
2018
Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo
Dominguez-Villar M, Raddassi K, Danielsen AC, Guarnaccia J, Hafler DA. Fingolimod modulates T cell phenotype and regulatory T cell plasticity in vivo. Journal Of Autoimmunity 2018, 96: 40-49. PMID: 30122421, PMCID: PMC7882197, DOI: 10.1016/j.jaut.2018.08.002.Peer-Reviewed Original ResearchConceptsT cellsMultiple sclerosisT cell effector phenotypeRelapsing-remitting multiple sclerosisRegulatory T cell populationTh1-like phenotypeRegulatory T cellsPro-inflammatory cytokinesT-cell phenotypeT cell populationsExpression of Th1Immune cell functionRegulatory T cell plasticityT cell plasticityCentral nervous systemExpression of markersCell migratory capacityImportant immunomodulatory functionsExcessive Th1Fingolimod treatmentExhaustion markersTh17 cytokinesEffector phenotypeLymph nodesSerum levels
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
2011
Interferon 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
A Randomized Controlled Double-Masked Trial of Albuterol Add-on Therapy in Patients With Multiple Sclerosis
Khoury SJ, Healy BC, Kivisäkk P, Viglietta V, Egorova S, Guttmann CR, Wedgwood JF, Hafler DA, Weiner HL, Buckle G, Cook S, Reddy S. A Randomized Controlled Double-Masked Trial of Albuterol Add-on Therapy in Patients With Multiple Sclerosis. JAMA Neurology 2010, 67: 1055-1061. PMID: 20837847, PMCID: PMC2954052, DOI: 10.1001/archneurol.2010.222.Peer-Reviewed Original ResearchMeSH KeywordsAdjuvants, ImmunologicAdrenergic beta-AgonistsAdultAlbuterolDouble-Blind MethodDrug Administration ScheduleDrug Therapy, CombinationFemaleGlatiramer AcetateHumansInterferon-gammaInterleukin-13Logistic ModelsMaleMiddle AgedMultiple Sclerosis, Relapsing-RemittingOdds RatioPeptidesPilot ProjectsTreatment OutcomeConceptsMultiple Sclerosis Functional CompositeRelapsing-remitting multiple sclerosisGlatiramer acetateMultiple sclerosisClinical trialsAlbuterol groupTime pointsOral doseIL-13Subcutaneous injectionHelper T-cell subtypes 1Double-masked clinical trialGlatiramer acetate treatmentImmunologic end pointsMasked clinical trialEffects of albuterolIL-12 expressionIL-13 productionStudy time pointsΒ2-adrenergic agonistAlbuterol treatmentAcetate therapyAdverse eventsFirst relapseImmunologic effects
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
2006
CHAPTER 46 Multiple Sclerosis
BRASS S, WEINER H, HAFLER D. CHAPTER 46 Multiple Sclerosis. 2006, 615-632. DOI: 10.1016/b978-012595961-2/50049-4.Peer-Reviewed Original ResearchSecondary progressive multiple sclerosisRelapsing-remitting multiple sclerosisPrimary progressive multiple sclerosisOligoclonal immunoglobulin bandsProgressive multiple sclerosisMultiple sclerosisCNS white matter tractSigns of MSTreatment of MSIncoordination of gaitCSF of patientsLoss of sensationWhite matter tractsOptic neuritisFiber involvementLimb weaknessMost patientsVisual lossClinical featuresImmunoglobulin bandsCommon symptomsImmunologic markersCorticospinal tractNormal glucoseAnimal models
2004
Cross-Reactive TCR Responses to Self Antigens Presented by Different MHC Class II Molecules
Mycko MP, Waldner H, Anderson DE, Bourcier KD, Wucherpfennig KW, Kuchroo VK, Hafler DA. Cross-Reactive TCR Responses to Self Antigens Presented by Different MHC Class II Molecules. The Journal Of Immunology 2004, 173: 1689-1698. PMID: 15265898, DOI: 10.4049/jimmunol.173.3.1689.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsAntigen PresentationAutoantigensCD4 AntigensCross ReactionsEncephalomyelitis, Autoimmune, ExperimentalHLA-DR alpha-ChainsHLA-DR AntigensHLA-DRB1 ChainsHumansHybridomasL CellsLymphocyte ActivationMembrane ProteinsMiceMolecular Sequence DataMultiple Sclerosis, Relapsing-RemittingMyelin Basic ProteinPeptide FragmentsPhosphorylationProtein Processing, Post-TranslationalReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaT-Lymphocyte SubsetsTransfectionConceptsAutoreactive T cellsMHC class II moleculesClass II moleculesT cellsSpontaneous experimental autoimmune encephalomyelitisRelapsing-remitting multiple sclerosisDifferent MHC class II moleculesExperimental autoimmune encephalomyelitisAltered peptide ligandTh cell clonesT cell hybridomasMyelin basic proteinAutoimmune encephalomyelitisMultiple sclerosisSelf antigensCD4 coreceptorRestriction elementsHealthy individualsDiseased patientsHuman TCRPatientsTCR responsesCell clonesCell hybridomasPeptide ligands
2001
Decreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis
Gausling R, Trollmo C, Hafler D. Decreases in Interleukin-4 Secretion by Invariant CD4−CD8−Vα24JαQ T Cells in Peripheral Blood of Patients with Relapsing–Remitting Multiple Sclerosis. Clinical Immunology 2001, 98: 11-17. PMID: 11141321, DOI: 10.1006/clim.2000.4942.Peer-Reviewed Original ResearchConceptsRelapsing-remitting multiple sclerosisT cell receptorIFN-gamma secretionMultiple sclerosisT cell clonesT cellsCytokine profilePeripheral bloodIL-4Cell clonesProgressive multiple sclerosisRR-MS patientsCytokine secretion patternsRelapsing-remitting MSInterleukin-4 secretionT cell functionalityCytokine secretionHealthy controlsSecretion patternPatientsCP-MSImmune systemControl individualsCell receptorSecretion
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