2015
Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins
Willis SN, Stathopoulos P, Chastre A, Compton SD, Hafler DA, O’Connor K. Investigating the Antigen Specificity of Multiple Sclerosis Central Nervous System-Derived Immunoglobulins. Frontiers In Immunology 2015, 6: 600. PMID: 26648933, PMCID: PMC4663633, DOI: 10.3389/fimmu.2015.00600.Peer-Reviewed Original ResearchCentral nervous systemB cell responsesMultiple sclerosisB cellsCNS tissueCerebrospinal fluidAntigen specificityNervous systemCell responsesAntigen-driven B cell responsesImmune cell infiltrationMS central nervous systemTertiary lymphoid structuresResident B cellsAntigen-driven responseB cell clonesMS brainsLymphoid structuresCell infiltrationRecombinant human immunoglobulinNeurofilament lightCNS-derived cell linesCandidate antigensAntigen arraysDisease pathology11C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas
Park E, Gallezot JD, Delgadillo A, Liu S, Planeta B, Lin SF, O’Connor K, Lim K, Lee JY, Chastre A, Chen MK, Seneca N, Leppert D, Huang Y, Carson RE, Pelletier D. 11C-PBR28 imaging in multiple sclerosis patients and healthy controls: test-retest reproducibility and focal visualization of active white matter areas. European Journal Of Nuclear Medicine And Molecular Imaging 2015, 42: 1081-1092. PMID: 25833352, DOI: 10.1007/s00259-015-3043-4.Peer-Reviewed Original ResearchConceptsNormal-appearing white matterVolume of distributionTest-retest variabilityWhole brain white matterHealthy controlsMicroglial activationTest-retest reproducibilityGray matterMultiple sclerosisMS subjectsWhite matterWhole brain gray matterGood test-retest reproducibilityAbsolute test-retest variabilityActive MS patientsPositron emission tomography (PET) ligandMultiple sclerosis patientsMain outcome measuresWhite matter areasMS WM lesionsBrain gray matterDemyelinating injuryTest-retest resultsVT valuesMS patients
2014
Chapter 52 Multiple Sclerosis
Hernandez A, O’Connor K, Hafler D. Chapter 52 Multiple Sclerosis. 2014, 735-756. DOI: 10.1016/b978-0-12-384929-8.00052-6.ChaptersMultiple sclerosisT cellsCell subsetsInflammatory autoimmune diseaseRegulatory T cellsT cell subsetsCNS white matterB cell subsetsImmune dysregulationTh1 subsetAutoimmune diseasesHumoral responseDisease evolutionInfectious agentsGenetic susceptibility lociProgressive neurodegenerationWhite matterCurrent diseaseGenetic riskDiseasePotential roleSclerosisSusceptible hostsTherapyPutative role
2013
Specific peripheral B cell tolerance defects in patients with multiple sclerosis
Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P, Herold KC, Hafler DA, O’Connor K, Meffre E. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. Journal Of Clinical Investigation 2013, 123: 2737-2741. PMID: 23676463, PMCID: PMC3668812, DOI: 10.1172/jci68775.Peer-Reviewed Original ResearchConceptsB cell tolerance checkpointsB cell tolerance defectsMultiple sclerosisRheumatoid arthritisTolerance checkpointsB cellsPeripheral B cell tolerance checkpointsTolerance defectsAutoreactive B cell clonesMature naive B cellsType 1 diabetesAutoreactive B cellsB cell toleranceCentral nervous systemNaive B cellsB cell clonesB cell selectionEarly B cell developmentIPEX patientsMost patientsTreg functionHomeostatic proliferationAutoimmune diseasesPatientsHealthy individualsSerum 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
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
2010
Elevated Intrathecal Myelin Oligodendrocyte Glycoprotein Antibodies in Multiple Sclerosis
Klawiter EC, Piccio L, Lyons JA, Mikesell R, O’Connor K, Cross AH. Elevated Intrathecal Myelin Oligodendrocyte Glycoprotein Antibodies in Multiple Sclerosis. JAMA Neurology 2010, 67: 1102-1108. PMID: 20837855, PMCID: PMC3051403, DOI: 10.1001/archneurol.2010.197.Peer-Reviewed Original ResearchConceptsMultiple sclerosisMyelin oligodendrocyte glycoproteinCerebrospinal fluidClinical disabilityMS patientsCSF markersAntibody productionForms of MSProspective case-controlled seriesMyelin oligodendrocyte glycoprotein antibodyDiagnosis of MSImmunoglobulin G indexNoninflammatory neurologic diseasesRoutine CSF testingProgressive multiple sclerosisAcademic referral centerRelapsing-remitting MSRadiographic outcome measuresMagnetic resonance metricsCase-control seriesReferral centerAlbumin levelsIgG indexCSF testingGlycoprotein antibodiesA unique antibody gene signature is prevalent in the central nervous system of patients with multiple sclerosis
Ligocki AJ, Lovato L, Xiang D, Guidry P, Scheuermann RH, Willis SN, Almendinger S, Racke MK, Frohman EM, Hafler DA, O'Connor KC, Monson NL. A unique antibody gene signature is prevalent in the central nervous system of patients with multiple sclerosis. Journal Of Neuroimmunology 2010, 226: 192-193. PMID: 20655601, PMCID: PMC2937103, DOI: 10.1016/j.jneuroim.2010.06.016.Peer-Reviewed Original ResearchConceptsMultiple sclerosisB cellsGene signatureMS brain tissueCSF of patientsCNS tissue samplesEnriched B cellsCentral nervous systemB cell receptorMS brainsTissue injuryNervous systemBrain tissueCell receptorTissue samplesSclerosisPatientsCSFUnique accumulationCellsSomatic hypermutationInjuryBrainReceptors
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
2006
Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers
O’Connor K, Roy SM, Becker CH, Hafler DA, Kantor AB. Comprehensive Phenotyping in Multiple Sclerosis: Discovery Based Proteomics and the Current Understanding of Putative Biomarkers. Disease Markers 2006, 22: 213-225. PMID: 17124343, PMCID: PMC3851054, DOI: 10.1155/2006/670439.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMultiple sclerosisMagnetic resonance imagingPutative biomarkersComprehensive phenotypingMonitoring of progressionComponent expression levelsClinical evaluationCSF proteinAccurate biomarkersCerebrospinal fluid chemistryControl groupTherapeutic interventionsPatient careAccurate diagnosisResonance imagingDisease pathologyFurther evaluationBiomarkersPreliminary dataExpression levelsSclerosisDiagnosisCSFSingle testNovel assessment
2005
Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein
O’Connor K, Appel H, Bregoli L, Call ME, Catz I, Chan JA, Moore NH, Warren KG, Wong SJ, Hafler DA, Wucherpfennig KW. Antibodies from Inflamed Central Nervous System Tissue Recognize Myelin Oligodendrocyte Glycoprotein. The Journal Of Immunology 2005, 175: 1974-1982. PMID: 16034142, PMCID: PMC4515951, DOI: 10.4049/jimmunol.175.3.1974.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAutoantibodiesBinding Sites, AntibodyCentral Nervous SystemDemyelinating Autoimmune Diseases, CNSFemaleFluoroimmunoassayHumansMaleMolecular Sequence DataMultiple SclerosisMyelin ProteinsMyelin-Associated GlycoproteinMyelin-Oligodendrocyte GlycoproteinRadioimmunoassaySolutionsConceptsMyelin oligodendrocyte glycoproteinMultiple sclerosisCNS diseaseOligodendrocyte glycoproteinCNS tissueChronic inflammatory CNS diseasesAutoantibody-mediated pathologyInflammatory CNS diseasesCentral nervous system tissueInflammatory CNS diseaseCases of encephalitisHigh-affinity autoantibodiesCases of subacuteNervous system tissueCNS parenchymaMOG autoantibodiesMS patientsOligodendrocyte lossMOG-AbCNS diseasesAutoantibodiesCerebrospinal fluidMOG proteinPostmortem casesControl tissuesMultiple sclerosis
Hafler DA, Slavik JM, Anderson DE, O'Connor KC, De Jager P, Baecher‐Allan C. Multiple sclerosis. Immunological Reviews 2005, 204: 208-231. PMID: 15790361, DOI: 10.1111/j.0105-2896.2005.00240.x.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMultiple sclerosisT cellsB cellsImmunopathology of MSCentral nervous system white matterNervous system white matterRegulatory T cellsHallmark of inflammationImmunosuppressive therapyAutoimmune processImmunomodulatory therapeuticsAnimal modelsMS researchWhite matterDisease pathologyClonal expansionDiseaseMajor histocompatibility complex (MHC) genesMolecular pathologyRNA expressionSclerosisInflammationTherapyPathologyComplex genetic diseases
2003
Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions
O'Connor KC, Chitnis T, Griffin DE, Piyasirisilp S, Bar-Or A, Khoury S, Wucherpfennig KW, Hafler DA. Myelin basic protein-reactive autoantibodies in the serum and cerebrospinal fluid of multiple sclerosis patients are characterized by low-affinity interactions. Journal Of Neuroimmunology 2003, 136: 140-148. PMID: 12620653, DOI: 10.1016/s0165-5728(03)00002-x.Peer-Reviewed Original ResearchConceptsMyelin basic proteinMultiple sclerosisCerebrospinal fluidSoluble myelin basic proteinSemple rabies vaccinePresence of autoantibodiesMultiple sclerosis patientsSera of patientsFraction of patientsAnti-MBP antibodiesHigh-affinity autoantibodiesBasic proteinMBP autoantibodiesRelevant autoantibodiesMS patientsSclerosis patientsAutoimmune diseasesHumoral responseRabies vaccineAutoantibodiesPatientsImmunodominant antigensSerumDiseaseSolid-phase assays
2001
The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis
O'connor K, Bar-Or A, Hafler D. The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis. Journal Of Clinical Immunology 2001, 21: 81-92. PMID: 11332657, DOI: 10.1023/a:1011064007686.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsMultiple sclerosisT cellsB cellsImmunopathology of MSMyelin-reactive T cellsCentral nervous system white matterNervous system white matterAutoreactive T cellsMS immunopathologyImmunosuppressive therapyCNS pathogenesisTolerance breakdownAutoreactive cellsInflammatory diseasesPathological studiesAnimal modelsB lymphocytesWhite matterMajor mediatorDisease pathologyNonhuman primatesDiseaseEvidence supportImmunopathologySclerosis