2019
Siponimod Chips Away at Progressive MS
Longbrake EE, Hafler DA. Siponimod Chips Away at Progressive MS. Cell 2019, 179: 1440. PMID: 31951523, PMCID: PMC8023412, DOI: 10.1016/j.cell.2019.11.034.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisGadolinium-enhancing MRI lesionsInflammatory disease activityImmunomodulatory medicationsDisability progressionDisease activityMRI lesionsProgressive MSNeurologic disabilityPMS patientsMultiple sclerosisSiponimodMedicationsSclerosisPatientsLesionsBedsideProgression
2011
Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis
Lovato L, Willis SN, Rodig SJ, Caron T, Almendinger SE, Howell OW, Reynolds R, O’Connor K, Hafler DA. Related B cell clones populate the meninges and parenchyma of patients with multiple sclerosis. Brain 2011, 134: 534-541. PMID: 21216828, PMCID: PMC3030766, DOI: 10.1093/brain/awq350.Peer-Reviewed Original ResearchConceptsB cell clonesB cell aggregatesMultiple sclerosisCentral nervous systemParenchymal infiltratesCell clonesNervous systemMeningeal B cell aggregatesRelated B cell clonesProgressive multiple sclerosisB-cell infiltratesCerebral spinal fluidInflammatory plaquesCell infiltrateImmune compartmentParenchymal lesionsLymphoid tissueSclerosisSpinal fluidWhite matterPatientsGray matterBrain tissueInfiltratesMeninges
2006
Innate Immunity in Multiple Sclerosis: Myeloid Dendritic Cells in Secondary Progressive Multiple Sclerosis Are Activated and Drive a Proinflammatory Immune Response
Karni A, Abraham M, Monsonego A, Cai G, Freeman GJ, Hafler D, Khoury SJ, Weiner HL. Innate Immunity in Multiple Sclerosis: Myeloid Dendritic Cells in Secondary Progressive Multiple Sclerosis Are Activated and Drive a Proinflammatory Immune Response. The Journal Of Immunology 2006, 177: 4196-4202. PMID: 16951385, DOI: 10.4049/jimmunol.177.6.4196.Peer-Reviewed Original ResearchConceptsMyeloid dendritic cellsDendritic cellsMultiple sclerosisInnate immune systemRR-MSImmune responseImmune systemT cell-mediated autoimmune diseaseSecondary progressive multiple sclerosisCell-mediated autoimmune diseaseStages of MSIncreased percentageProgressive phaseNeuronal degenerative changesSecondary progressive phaseSP-MS patientsProgressive multiple sclerosisProinflammatory immune responsePrimary immune responseNaive T cellsImmunologic basisTh1 responseClinical patternMS patientsPD-L1CHAPTER 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
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
1999
Treatment of progressive multiple sclerosis with pulse cyclophosphamidel methylprednisolone: Response to therapy is linked to the duration of progressive disease
Hohol M, Olek M, Orav E, Stazzone L, Hafler D, Khoury S, Dawson D, Weiner H. Treatment of progressive multiple sclerosis with pulse cyclophosphamidel methylprednisolone: Response to therapy is linked to the duration of progressive disease. Multiple Sclerosis Journal 1999, 5: 403-409. PMID: 10618696, DOI: 10.1177/135245859900500i606.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisDuration of progressionMultiple sclerosisProgressive diseaseSecondary progressive multiple sclerosisDuration of MSPrimary progressive patientsProgressive MS patientsPositive clinical responseOpen-label fashionClinical outcome measuresStart of treatmentOnset of diseaseMethylprednisolone therapySecondary progressiveImmunomodulatory treatmentImmunosuppressive therapyProgressive patientsClinical responsePatient characteristicsMS patientsImmunosuppressive agentsAutoimmune diseasesLabel fashionEDSS changeTreatment of progressive multiple sclerosis with pulse cyclophosphamide/methylprednisolone: Response to therapy is linked to the duration of progressive disease
Hohol M, Olek M, John Orav E, Stazzone L, Hafler D, Khoury S, Dawson D, Weiner H. Treatment of progressive multiple sclerosis with pulse cyclophosphamide/methylprednisolone: Response to therapy is linked to the duration of progressive disease. Multiple Sclerosis Journal 1999, 5: 403-409. DOI: 10.1191/135245899678846492.Peer-Reviewed Original ResearchProgressive multiple sclerosisProgressive diseaseMultiple sclerosisMethylprednisoloneSclerosisTherapyDisease
1998
Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis
Windhagen A, Anderson DE, Carrizosa A, Balashov K, Weiner HL, Hafler DA. Cytokine secretion of myelin basic protein reactive T cells in patients with multiple sclerosis. Journal Of Neuroimmunology 1998, 91: 1-9. PMID: 9846813, DOI: 10.1016/s0165-5728(98)00086-1.Peer-Reviewed Original ResearchConceptsMBP-reactive T cellsReactive T cellsChronic progressive multiple sclerosisProgressive multiple sclerosisMultiple sclerosisT cellsCytokine secretionMyelin basic proteinT cell linesNormal controlsMyelin basic protein-reactive T cellsAntigen-specific cytokine secretionMyelin-reactive T cellsNormal individualsShort-term T cell linesAutoreactive T cell linesCP MS patientsIL-12/IL-4/MBP-reactive cellsTh2-type phenotypeRR-MS patientsTh2 cytokine secretionAutoreactive T cellsMore IFN-gamma
1997
Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand
Balashov K, Smith D, Khoury S, Hafler D, Weiner H. Increased interleukin 12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 599-603. PMID: 9012830, PMCID: PMC19559, DOI: 10.1073/pnas.94.2.599.Peer-Reviewed Original ResearchConceptsIL-12 secretionIFN-gamma secretionMS patientsMultiple sclerosisT cellsIL-12Anti-CD40 ligand antibodyTh1-type immune activationCell-mediated autoimmune diseaseProgressive MS patientsProgressive multiple sclerosisIFN-gamma administrationRelapsing-remitting patientsExacerbation of diseaseInterleukin-12 productionChronic inflammatory diseaseCD40 ligand expressionCentral nervous systemActivated T cellsImmune interventionImmune activationAutoimmune diseasesInterleukin-12Inflammatory diseasesCD40 ligand
1996
Increased IL-12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand
Weiner H, Balashov K, Smith D, Khoury S, Hafler D. Increased IL-12 production in progressive multiple sclerosis: Induction by activated CD4+ T cells via CD40 ligand. Multiple Sclerosis Journal 1996, 2: 253-253. DOI: 10.1177/135245859600200519.Peer-Reviewed Original Research
1995
Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis.
Balashov KE, Khoury SJ, Hafler DA, Weiner HL. Inhibition of T cell responses by activated human CD8+ T cells is mediated by interferon-gamma and is defective in chronic progressive multiple sclerosis. Journal Of Clinical Investigation 1995, 95: 2711-2719. PMID: 7769110, PMCID: PMC295954, DOI: 10.1172/jci117973.Peer-Reviewed Original ResearchConceptsAutologous mixed lymphocyte reactionProgressive multiple sclerosisChronic progressive multiple sclerosisInduction of CD8Tact cellsMultiple sclerosisT cellsHuman CD8Suppressive propertiesAutologous T cellsRelapsing-remitting MST cell responsesHuman autoimmune diseasesMixed lymphocyte reactionGM-CSF antibodySuppressive CD8Autologous antigenLymphocyte reactionAutoimmune diseasesBeta antibodyGamma antibodyCD8Proliferative responseSpecific cytokinesNormal controls
1993
Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group.
Weiner HL, Mackin GA, Orav EJ, Hafler DA, Dawson DM, LaPierre Y, Herndon R, Lehrich JR, Hauser SL, Turel A, Fisher M, Birnbaum G, McArthur J, Butler R, Moore M, Sigsbee B, Safran A. Intermittent cyclophosphamide pulse therapy in progressive multiple sclerosis: final report of the Northeast Cooperative Multiple Sclerosis Treatment Group. Neurology 1993, 43: 910-8. PMID: 8388090, DOI: 10.1212/wnl.43.5.910.Peer-Reviewed Original ResearchConceptsMajority of patientsInduction regimenTreatment failureTreatment groupsCyclophosphamide pulse therapyPatients 40 yearsPatients ages 41Progressive MS patientsPulse cyclophosphamide therapyPatients age 18Progressive multiple sclerosisNonbooster groupPulse therapyCyclophosphamide therapyProgressive MSMS patientsMultiple sclerosisDisease progressionSignificant benefitsAge 41Subsequent progressionPatientsInitial stabilizationAge 18Regimen
1992
T cell vaccination in multiple sclerosis: A preliminary report
Hafler D, Cohen I, Benjamin D, Weiner H. T cell vaccination in multiple sclerosis: A preliminary report. Clinical Immunology 1992, 62: 307-313. PMID: 1541056, DOI: 10.1016/0090-1229(92)90108-z.Peer-Reviewed Original ResearchConceptsT cell clonesMultiple sclerosisAutoimmune diseasesCell clonesAutologous T cell clonesAutoreactive T cell clonesAutologous mixed lymphocyte responseProgressive multiple sclerosisExperimental autoimmune diseasesT cell vaccinationFurther clinical trialsMixed lymphocyte responseUntoward side effectsCentral nervous systemPhase one trialsCell vaccinationMyelin autoantigensImmunologic effectsLymphocyte responsesClinical trialsImmunologic studiesAutoreactive clonesCerebrospinal fluidSide effectsNervous system
1991
Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis
Hafler D, Orav J, Gertz R, Stazzone L, Weiner H. Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis. Journal Of Neuroimmunology 1991, 32: 149-158. PMID: 1672870, DOI: 10.1016/0165-5728(91)90007-t.Peer-Reviewed Original ResearchConceptsT cell populationsDisability Status ScaleMixed lymphocyte reactionSpontaneous proliferationT cellsImmune measuresACTH infusionImmune functionChronic progressive multiple sclerosisProgressive multiple sclerosis patientsCD4/CD8 ratioCell populationsAllogeneic mixed lymphocyte reactionFunctional immune measuresPeripheral blood CD4Progressive multiple sclerosisPositive clinical responsePositive T cellsMultiple sclerosis patientsFunctional immune assaysLevels of proliferationBlood CD4CD8 ratioClinical improvementClinical responseInterleukin-1 corrects the defective autologous mixed lymphocyte response in multiple sclerosis
Hafler D, Chofflon M, Kurt-Jones E, Weiner H. Interleukin-1 corrects the defective autologous mixed lymphocyte response in multiple sclerosis. Clinical Immunology 1991, 58: 115-125. PMID: 1670583, DOI: 10.1016/0090-1229(91)90153-2.Peer-Reviewed Original ResearchConceptsAutologous mixed lymphocyte reactionMultiple sclerosisWhole T cellsMS patientsT cellsImmune defectsChronic progressive multiple sclerosisNon-T cell populationsAutologous mixed lymphocyte responseProgressive multiple sclerosisMixed lymphocyte responseMixed lymphocyte reactionResponse of CD4T cell populationsSex-matched controlsT cell regulationIL-1 secretionCell populationsLymphokine IFN-gammaImmunoregulatory defectsLymphocyte responsesRIL-2Lymphocyte reactionMS subjectsAutoimmune diseases
1989
MS: a CNS and systematic autoimmune disease
Hafler D, Weiner H. MS: a CNS and systematic autoimmune disease. Trends In Immunology 1989, 10: 104-107. PMID: 2472810, DOI: 10.1016/0167-5699(89)90236-3.Peer-Reviewed Original ResearchConceptsPeripheral immune compartmentCentral nervous systemImmune compartmentMultiple sclerosisImmunoregulatory defectsMS patientsAutoimmune diseasesCNS inflammatory responsesTotal lymphoid irradiationProgressive multiple sclerosisT-cell abnormalitiesB cell hyperactivitySystemic lupus erythematosusT cell functionSystematic autoimmune diseaseActivated T cellsLymphoid irradiationDisease activityImmune abnormalitiesSystemic treatmentLupus erythematosusRheumatoid arthritisPeripheral bloodInflammatory diseasesInflammatory response
1988
Cumulative Experience with High‐Dose Intravenous Cyclophosphamide and ACTH Therapy in Chronic Progressive Multiple Sclerosis
CARTER J, DAWSON D, HAFLER D, FALLIS R, STAZZONE L, ORAV J, WEINER H. Cumulative Experience with High‐Dose Intravenous Cyclophosphamide and ACTH Therapy in Chronic Progressive Multiple Sclerosis. Annals Of The New York Academy Of Sciences 1988, 540: 535-536. PMID: 2849902, DOI: 10.1111/j.1749-6632.1988.tb27163.x.Peer-Reviewed Original ResearchLoss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis
Chofflon M, Weiner H, Morimoto C, Hafler D. Loss of functional suppression is linked to decreases in circulating suppressor inducer (CD4 + 2H4 +) T Cells in multiple sclerosis. Annals Of Neurology 1988, 24: 185-191. PMID: 2972249, DOI: 10.1002/ana.410240203.Peer-Reviewed Original ResearchConceptsSuppressor-inducer T cellsProgressive multiple sclerosisInducer T cellsSuppressor T cellsMultiple sclerosisT cellsFunctional suppressionTwo-color immunofluorescenceImmunoregulatory abnormalitiesImmunological findingsIgG synthesisMononuclear cellsPokeweed mitogenImmunoglobulin synthesisNormal subjectsSclerosisCD4Neurological diseasesAMLRPatientsTwo-stage assaySuppressor functionSignificant correlationPresent studyCellsAnti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis. Immunosuppressive effects and human anti-mouse responses.
Hafler DA, Ritz J, Schlossman SF, Weiner HL. Anti-CD4 and anti-CD2 monoclonal antibody infusions in subjects with multiple sclerosis. Immunosuppressive effects and human anti-mouse responses. The Journal Of Immunology 1988, 141: 131-8. PMID: 2454256, DOI: 10.4049/jimmunol.141.1.131.Peer-Reviewed Original ResearchConceptsHuman anti-mouse antibodiesAnti-mouse responseAnti-mouse antibodiesHuman anti-mouse responseMultiple sclerosisChronic progressive multiple sclerosisPhase I clinical studyAnti-CD2 monoclonal antibodiesProgressive multiple sclerosisMore chronic diseasesT cell subpopulationsHuman immune responseT cell activationAcute immunosuppressionMAb infusionsT cell surfaceAnti-CD4Daily infusionsImmunologic responseImmunosuppressive effectsChronic diseasesIgG isotypeClinical studiesImmune responseLike antibodiesImmunosuppression with high-dose i.v. cyclophosphamide and ACTH in progressive multiple sclerosis: cumulative 6-year experience in 164 patients.
Carter JL, Hafler DA, Dawson DM, Orav J, Weiner HL. Immunosuppression with high-dose i.v. cyclophosphamide and ACTH in progressive multiple sclerosis: cumulative 6-year experience in 164 patients. Neurology 1988, 38: 9-14. PMID: 2838768.Peer-Reviewed Original ResearchConceptsProgressive multiple sclerosisChronic progressive multiple sclerosisMultiple sclerosisShorter disease durationMajority of patientsDosage of medicationCurrent treatment programsInduction regimenComplication rateDisease durationFrequent complicationLate complicationsYounger patientsPermanent remissionTreatment regimenInitial treatmentBooster injectionMaintenance treatmentMinor infectionsPatientsRemissionTreatment programRegimenComplicationsSingle treatment