2022
Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions
Zinger N, Ponath G, Sweeney E, Nguyen TD, Lo CH, Diaz I, Dimov A, Teng L, Zexter L, Comunale J, Wang Y, Pitt D, Gauthier SA. Dimethyl Fumarate Reduces Inflammation in Chronic Active Multiple Sclerosis Lesions. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e1138. PMID: 35046083, PMCID: PMC8771666, DOI: 10.1212/nxi.0000000000001138.Peer-Reviewed Original ResearchConceptsChronic active lesionsGlatiramer acetateRim lesionsHuman microgliaDimethyl fumarateMultiple sclerosisActive lesionsChronic active multiple sclerosis lesionsEffects of DMFActive multiple sclerosis lesionsClass III evidenceMarkers of inflammationRelapsing-remitting MSRetrospective observational studyQuantitative susceptibility mappingMultiple sclerosis lesionsActivation stateTreatment-induced changesMRI quantitative susceptibility mappingMicroglial activityGlial activityInflammatory activationMicroglial cellsObservational studyMS lesions
2021
QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions
Gillen KM, Mubarak M, Park C, Ponath G, Zhang S, Dimov A, Levine‐Ritterman M, Toro S, Huang W, Amici S, Kaunzner UW, Gauthier SA, Guerau‐de‐Arellano M, Wang Y, Nguyen TD, Pitt D. QSM is an imaging biomarker for chronic glial activation in multiple sclerosis lesions. Annals Of Clinical And Translational Neurology 2021, 8: 877-886. PMID: 33704933, PMCID: PMC8045922, DOI: 10.1002/acn3.51338.Peer-Reviewed Original ResearchConceptsNormal-appearing white matterMyeloid cellsLesion rimReactive oxygen speciesQuantitative susceptibility mappingChronic active lesionsChronic glial activationPro-inflammatory cytokinesBlood-brain barrierWhite matter lesionsAdjacent normal-appearing white matterMultiple sclerosis lesionsGlial activationActivated microgliaHistopathological correlatesChronic inflammationActive lesionsCytokine productionMatter lesionsMS lesionsWhite matterHuman-induced pluripotent stem cellsSclerosis lesionsLesionsLesion perimeter
2020
Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS
Lucca LE, Lerner BA, Park C, DeBartolo D, Harnett B, Kumar VP, Ponath G, Raddassi K, Huttner A, Hafler DA, Pitt D. Differential expression of the T-cell inhibitor TIGIT in glioblastoma and MS. Neurology Neuroimmunology & Neuroinflammation 2020, 7: e712. PMID: 32269065, PMCID: PMC7188477, DOI: 10.1212/nxi.0000000000000712.Peer-Reviewed Original ResearchConceptsTumor-infiltrating T cellsT cellsPD-1/PD-L1Anti-TIGIT therapyExpression of CD226Expression of TIGITPostmortem CNS tissueLymphocytes of patientsFresh surgical resectionsLigand CD155TIGIT expressionSurgical resectionPD-1PD-L1CNS diseaseHealthy controlsHealthy donorsLymphocytic expressionImmune responseCNS tissueMS lesionsTIGITImmune pathwaysPatientsGlioblastoma multiforme
2019
The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions
Park C, Ponath G, Levine-Ritterman M, Bull E, Swanson EC, De Jager PL, Segal BM, Pitt D. The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions. Acta Neuropathologica Communications 2019, 7: 130. PMID: 31405387, PMCID: PMC6689891, DOI: 10.1186/s40478-019-0779-2.Peer-Reviewed Original ResearchConceptsMultiple sclerosis lesionsLesion rimAstrocyte phenotypeMyeloid cellsSclerosis lesionsActive multiple sclerosis lesionsAcute multiple sclerosis lesionsGlial activation markersActive MS lesionsNovel therapeutic targetDifferent lesion stagesPredominant cell typeAcute demyelinationDemyelinating lesionsCell typesActivation markersChronic inflammationDistinct myeloidCell-extrinsic factorsGlial cellsPhenotypic subsetsLesion stageGlial phenotypeMS lesionsLesion cellsMultiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
Ramaglia V, Sheikh-Mohamed S, Legg K, Park C, Rojas OL, Zandee S, Fu F, Ornatsky O, Swanson EC, Pitt D, Prat A, McKee TD, Gommerman JL. Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry. ELife 2019, 8: e48051. PMID: 31368890, PMCID: PMC6707785, DOI: 10.7554/elife.48051.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMS disease activityT-cell phenotypeMass cytometryTypes of lymphocytesMultiple sclerosis lesionsNatalizumab cessationDisease activityMS patientsInflammatory lesionsImmune cellsSpinal cordLesion morphometryMS lesionsB cellsLesion typeSclerosis lesionsLesionsBlood vesselsCell phenotypeFunctional stateCytometryCellular contentCell-cell interactionsPhenotype
2018
Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis
Ponath G, Lincoln MR, Levine-Ritterman M, Park C, Dahlawi S, Mubarak M, Sumida T, Airas L, Zhang S, Isitan C, Nguyen TD, Raine CS, Hafler DA, Pitt D. Enhanced astrocyte responses are driven by a genetic risk allele associated with multiple sclerosis. Nature Communications 2018, 9: 5337. PMID: 30559390, PMCID: PMC6297228, DOI: 10.1038/s41467-018-07785-8.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAstrocyte responseRisk variantsLocal autoimmune inflammationPeripheral immune cellsCentral nervous system cellsPeripheral immune systemCultured human astrocytesNervous system cellsNF-κB signalingCNS accessDysfunctional lymphocytesAstroglial functionAutoimmune inflammationLymphocytic infiltrateLymphocyte recruitmentImmune cellsGenetic risk allelesGenetic risk variantsMS lesionsMS susceptibilityHuman astrocytesLesion sizeImmune systemSystem cellsThe Role of Astrocytes in Multiple Sclerosis
Ponath G, Park C, Pitt D. The Role of Astrocytes in Multiple Sclerosis. Frontiers In Immunology 2018, 9: 217. PMID: 29515568, PMCID: PMC5826071, DOI: 10.3389/fimmu.2018.00217.Peer-Reviewed Original ResearchConceptsRole of astrocytesImmune cell accessCentral nervous systemMultiple sclerosis lesionsAstrocyte activationMultiple sclerosisGlial scarAstrocyte functionMS treatmentMS lesionsNervous systemAstrocytesSclerosis lesionsLesion formationFunctional polarizationLesionsCell accessSclerosisInflammationPathogenesisMyeloid cell plasticity in the evolution of central nervous system autoimmunity
Giles DA, Washnock‐Schmid J, Duncker PC, Dahlawi S, Ponath G, Pitt D, Segal BM. Myeloid cell plasticity in the evolution of central nervous system autoimmunity. Annals Of Neurology 2018, 83: 131-141. PMID: 29283442, PMCID: PMC5876132, DOI: 10.1002/ana.25128.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginaseAutoimmune Diseases of the Nervous SystemBone Marrow CellsCell PlasticityChimeraDisease ProgressionEncephalomyelitis, Autoimmune, ExperimentalHumansImmunohistochemistryLectins, C-TypeMannose ReceptorMannose-Binding LectinsMiceMice, Inbred C57BLMultiple SclerosisMyeloid CellsNitric Oxide Synthase Type IIPhenotypeReceptors, Cell SurfaceConceptsInducible nitric oxide synthaseExperimental autoimmune encephalomyelitisCNS myeloid cellsCentral nervous systemCentral nervous system autoimmunityChronic active MS lesionsActive MS lesionsMultiple sclerosisMyeloid cellsMS lesionsAnimal model experimental autoimmune encephalomyelitisRemission of EAEModel experimental autoimmune encephalomyelitisMyeloid cell plasticityEncephalitogenic T cellsNitric oxide synthaseMyeloid cell phenotypeFuture therapeutic strategiesHuman myeloid cellsAnn NeurolNoninflammatory phenotypePolarized subsetsClinical remissionAutoimmune encephalomyelitisProinflammatory markers
2016
Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation
Zhang Y, Gauthier SA, Gupta A, Chen W, Comunale J, Chiang G, Zhou D, Askin G, Zhu W, Pitt D, Wang Y. Quantitative Susceptibility Mapping and R2* Measured Changes during White Matter Lesion Development in Multiple Sclerosis: Myelin Breakdown, Myelin Debris Degradation and Removal, and Iron Accumulation. American Journal Of Neuroradiology 2016, 37: 1629-1635. PMID: 27256856, PMCID: PMC5018433, DOI: 10.3174/ajnr.a4825.Peer-Reviewed Original ResearchConceptsMyelin breakdownQuantitative susceptibility mappingExpanded Disability Status Scale scoreEarly active MS lesionsDisability Status Scale scoreIron accumulationDifferent enhancing patternStatus Scale scoreActive MS lesionsWhite matter lesionsMultiple sclerosis lesionsDisease durationChronic lesionsEarly chronicMatter lesionsMultiple sclerosisActive lesionsMyelin debrisMS lesionsLesion changesScale scoreLesion typeSclerosis lesionsLesionsLesion development
2014
Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron
Wisnieff C, Ramanan S, Olesik J, Gauthier S, Wang Y, Pitt D. Quantitative susceptibility mapping (QSM) of white matter multiple sclerosis lesions: Interpreting positive susceptibility and the presence of iron. Magnetic Resonance In Medicine 2014, 74: 564-570. PMID: 25137340, PMCID: PMC4333139, DOI: 10.1002/mrm.25420.Peer-Reviewed Original ResearchConceptsMultiple sclerosisQuantitative susceptibility mappingIron depositionMS brain tissueMicroglia/macrophagesWhite matter multiple sclerosis lesionsPresence of myelinMultiple sclerosis lesionsSubstantial iron depositionChronic inflammationMS lesionsSclerosis lesionsLesionsBrain tissueMyelinMicroglia
2013
Quantitative Susceptibility Mapping of Multiple Sclerosis Lesions at Various Ages
Chen W, Gauthier SA, Gupta A, Comunale J, Liu T, Wang S, Pei M, Pitt D, Wang Y. Quantitative Susceptibility Mapping of Multiple Sclerosis Lesions at Various Ages. Radiology 2013, 271: 183-92. PMID: 24475808, PMCID: PMC4263629, DOI: 10.1148/radiol.13130353.Peer-Reviewed Original ResearchConceptsNormal-appearing white matterMS lesionsMultiple sclerosis lesionsEnhanced lesionsQuantitative susceptibility mappingMR examinationsSclerosis lesionsConventional magnetic resonance imagingMagnetic resonance imagingT2-weighted imagesMS patientsPathophysiologic featuresCerebrospinal fluidOnline supplemental materialWhite matterLesionsQSM imagesResonance imagingPatientsMR imagingThree-dimensional gradient-echo sequenceGradient echo sequenceMonthsBonferroni correctionAge
2001
Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage
Werner P, Pitt D, Raine C. Multiple sclerosis: Altered glutamate homeostasis in lesions correlates with oligodendrocyte and axonal damage. Annals Of Neurology 2001, 50: 169-180. PMID: 11506399, DOI: 10.1002/ana.1077.Peer-Reviewed Original ResearchConceptsMultiple sclerosisAxonal damageWhite matterGlutamate excitotoxicityGlutamate homeostasisMS lesionsGlutaminase expressionMS white matterInflammatory neurologic diseasesActive MS lesionsCNS cell typesOligodendroglial pathologyNoninflammatory conditionsDystrophic axonsNeurologic diseaseGLT-1Low-level expressionAnimal modelsGlutamate transportersHomeostasis contributesLesion correlatesGlutamate transportLesionsOligodendrocytesTherapeutic import
1999
Neuregulin and erbB receptor expression in normal and diseased human white matter
Cannella B, Pitt D, Marchionni M, Raine C. Neuregulin and erbB receptor expression in normal and diseased human white matter. Journal Of Neuroimmunology 1999, 100: 233-242. PMID: 10695733, DOI: 10.1016/s0165-5728(99)00201-5.Peer-Reviewed Original ResearchConceptsGlial growth factor 2Multiple sclerosisErbB receptor expressionWhite matterHuman white matterReceptor expressionCases of MSHuman lymph node tissueAreas of remyelinationLymph node tissueGrowth factor 2Autoimmune demyelinationMicroglial cellsNeurologic diseaseMS lesionsNode tissueMitogenic effectWestern blotWestern blottingOligodendrocytesReceptorsRemyelinationWidespread expressionFactor 2Lymphocytes