2024
A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases.
Yandamuri S, Filipek B, Lele N, Cohen I, Bennett J, Nowak R, Sotirchos E, Longbrake E, Mace E, O'Connor K. A Noncanonical CD56dimCD16dim/- NK Cell Subset Indicative of Prior Cytotoxic Activity Is Elevated in Patients with Autoantibody-Mediated Neurologic Diseases. The Journal Of Immunology 2024, 212: 785-800. PMID: 38251887, PMCID: PMC10932911, DOI: 10.4049/jimmunol.2300015.Peer-Reviewed Original ResearchConceptsNeuromyelitis optica spectrum disorderAb-dependent cellular cytotoxicityNK cellsMyasthenia gravisMG patientsInduced Ab-dependent cellular cytotoxicityNK cell-mediated effector functionsPeripheral blood immune cell populationsCell-mediated effector functionsNeuromyelitis optica spectrum disorder patientsBlood immune cell populationsAb-dependent cellular cytotoxicity activityNK marker CD56NK cell markersHLA-DR expressionNK cell subsetsExpression of perforinImmune cell populationsAutoimmune myasthenia gravisElevated disease burdenHLA-DRCell subsetsCellular cytotoxicityChemokine receptorsMultiparameter immunophenotyping
2022
Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy
Fichtner ML, Hoehn KB, Ford EE, Mane-Damas M, Oh S, Waters P, Payne AS, Smith ML, Watson CT, Losen M, Martinez-Martinez P, Nowak RJ, Kleinstein SH, O’Connor K. Reemergence of pathogenic, autoantibody-producing B cell clones in myasthenia gravis following B cell depletion therapy. Acta Neuropathologica Communications 2022, 10: 154. PMID: 36307868, PMCID: PMC9617453, DOI: 10.1186/s40478-022-01454-0.Peer-Reviewed Original ResearchConceptsB cell depletion therapyB cell clonesMuSK-MG patientsMyasthenia gravisB cellsMG patientsDepletion therapyCell clonesAutoantibody-producing B cellsMuscle-specific tyrosine kinaseComplete stable remissionB cell receptor repertoireCell receptor repertoireValuable candidate biomarkersB cell receptorMG relapseClinical relapseStable remissionDisease relapseAutoimmune disordersRelapsePatientsAcetylcholine receptorsCandidate biomarkersReceptor repertoireNovel pathophysiological insights in autoimmune myasthenia gravis
Masi G, O’Connor K. Novel pathophysiological insights in autoimmune myasthenia gravis. Current Opinion In Neurology 2022, 35: 586-596. PMID: 35942663, PMCID: PMC9458626, DOI: 10.1097/wco.0000000000001088.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsAutoimmune myasthenia gravisMyasthenia gravisMG patientsClinical responseMuscle-specific tyrosine kinaseSpecific therapeutic strategiesNovel pathophysiological insightsMG pathologyMG subtypesAutoantibody repertoireTreatment optionsCancer immunotherapyPredictive biomarkersSuch therapyImmunological heterogeneityPathophysiological insightsMG phenotypeTherapeutic strategiesClinical observationsTherapeutic outcomesAcetylcholine receptorsDisease subtypesTherapeutic perspectivesSubtypesDevelopment of assaysHeterogeneity of Acetylcholine Receptor Autoantibody–Mediated Complement Activity in Patients With Myasthenia Gravis
Obaid AH, Zografou C, Vadysirisack DD, Munro-Sheldon B, Fichtner ML, Roy B, Philbrick WM, Bennett JL, Nowak RJ, O'Connor KC. Heterogeneity of Acetylcholine Receptor Autoantibody–Mediated Complement Activity in Patients With Myasthenia Gravis. Neurology Neuroimmunology & Neuroinflammation 2022, 9: e1169. PMID: 35473886, PMCID: PMC9128035, DOI: 10.1212/nxi.0000000000001169.Peer-Reviewed Original ResearchConceptsAChR autoantibodiesMyasthenia gravisDisease burdenComplement activityAcetylcholine receptor autoantibodiesAChR-MG patientsComplement inhibitor therapyLower autoantibody levelsClinical disease scoresSubset of patientsHealthy donor samplesCell-based assaysMost patient samplesMembrane attack complex formationModest positive associationMG subtypesAutoantibody levelsAutoantibody titersComplement membrane attack complex formationMG patientsInhibitor therapyReceptor autoantibodiesHD groupTherapeutic responseMAC formationThe clinical need for clustered AChR cell-based assay testing of seronegative MG
Masi G, Li Y, Karatz T, Pham MC, Oxendine SR, Nowak RJ, Guptill JT, O'Connor KC. The clinical need for clustered AChR cell-based assay testing of seronegative MG. Journal Of Neuroimmunology 2022, 367: 577850. PMID: 35366559, PMCID: PMC9106915, DOI: 10.1016/j.jneuroim.2022.577850.Peer-Reviewed Original ResearchConceptsSNMG patientsMyasthenia gravisAChR-specific B cellsClinical needAcetylcholine receptor autoantibodiesSeronegative MG patientsSeronegative myasthenia gravisCell-based assaysAutoantibody positivityTrial eligibilityMG patientsReceptor autoantibodiesPatientsB cellsU.S. CentersNew treatmentsAssaysGravisAutoantibodiesSerostatusAChRPositivity
2020
Immunoregulatory Cells in Myasthenia Gravis
Wu Y, Luo J, Garden O. Immunoregulatory Cells in Myasthenia Gravis. Frontiers In Neurology 2020, 11: 593431. PMID: 33384654, PMCID: PMC7769807, DOI: 10.3389/fneur.2020.593431.Peer-Reviewed Original ResearchMyeloid-derived suppressor cellsExperimental autoimmune MGMG patientsImmunoregulatory cellsCD4<sup>+</sup>Foxp3<sup>+</sup> regulatory T cellsCD4<sup>+</sup>Foxp3<sup>+</sup> TregsFoxp3<sup>+</sup> regulatory T cellsIL-10-producing B cellsPopulations of immunoregulatory cellsFollicular T helper cellsBiomarkers of disease activityFoxP3<sup>+</sup> TregsRegulatory T cellsImmunoregulatory cell populationsT helper cellsB-cell mediated autoimmune diseasesPathogenesis of MGHuman peripheral bloodContext of MGFollicular TregsAdoptive transferSuppressor cellsAutoimmune MGPeripheral bloodT cellsAutoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology
Fichtner ML, Jiang R, Bourke A, Nowak RJ, O’Connor K. Autoimmune Pathology in Myasthenia Gravis Disease Subtypes Is Governed by Divergent Mechanisms of Immunopathology. Frontiers In Immunology 2020, 11: 776. PMID: 32547535, PMCID: PMC7274207, DOI: 10.3389/fimmu.2020.00776.Peer-Reviewed Original ResearchConceptsLipoprotein receptor-related protein 4Chronic inflammatory demyelinating polyneuropathyMuSK myasthenia gravisMyasthenia gravisDisease subtypesPathogenic autoantibodiesNeuromyelitis opticaPemphigus vulgarisFab-arm exchangeNeuromuscular junctionAChR myasthenia gravisDistinct immune mechanismsInflammatory demyelinating polyneuropathyAutoimmune myasthenia gravisContribution of complementMuscle-specific kinaseNicotinic acetylcholine receptorsSubtype of diseaseDemyelinating polyneuropathyMG subtypesMG patientsAutoantibody productionClinical benefitAutoimmune diseasesAutoimmune pathologyExploring outcomes and characteristics of myasthenia gravis: Rationale, aims and design of registry – The EXPLORE-MG registry
Anil R, Kumar A, Alaparthi S, Sharma A, Nye JL, Roy B, O'Connor KC, Nowak RJ. Exploring outcomes and characteristics of myasthenia gravis: Rationale, aims and design of registry – The EXPLORE-MG registry. Journal Of The Neurological Sciences 2020, 414: 116830. PMID: 32388060, DOI: 10.1016/j.jns.2020.116830.Peer-Reviewed Original ResearchConceptsMyasthenia gravisMG patientsContemporary patient cohortKey clinical featuresMuscle-specific kinaseMG clinicClinical featuresGeneralized diseaseOutcomes RegistryPatient cohortPatient outcomesTreatment responsivenessTreatment outcomesTreatment strategiesRegistry dataEpidemiological dataInterim analysisData registryOcular diseasesPatientsCommon data elementsAcetylcholine receptorsRegistryPatient careDiseaseDifferential response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study
Litchman T, Roy B, Kumar A, Sharma A, Njike V, Nowak RJ. Differential response to rituximab in anti-AChR and anti-MuSK positive myasthenia gravis patients: a single-center retrospective study. Journal Of The Neurological Sciences 2020, 411: 116690. PMID: 32028072, DOI: 10.1016/j.jns.2020.116690.Peer-Reviewed Original ResearchConceptsMyasthenia gravisMGFA classRetrospective studyPositive myasthenia gravis patientsSingle-center retrospective studyManagement of MGAcetylcholine receptor autoantibodiesRefractory myasthenia gravisSymptom-free stateB-cell depletionMyasthenia gravis patientsClinical remissionClinical improvementDurable responsesMG patientsGravis patientsReceptor autoantibodiesMore hospitalizationsClinical symptomsExamination findingsCell depletionTreatment responsePatientsRituximabB cells
2019
Characterization of pathogenic monoclonal autoantibodies derived from muscle-specific kinase myasthenia gravis patients
Takata K, Stathopoulos P, Cao M, Mané-Damas M, Fichtner ML, Benotti ES, Jacobson L, Waters P, Irani SR, Martinez-Martinez P, Beeson D, Losen M, Vincent A, Nowak RJ, O’Connor K. Characterization of pathogenic monoclonal autoantibodies derived from muscle-specific kinase myasthenia gravis patients. JCI Insight 2019, 4: e127167. PMID: 31217355, PMCID: PMC6629167, DOI: 10.1172/jci.insight.127167.Peer-Reviewed Original ResearchConceptsMyasthenia gravisMonoclonal autoantibodiesNeuromuscular junctionMuscle-specific tyrosine kinaseMuSK-MG patientsChronic autoimmune disorderMyasthenia gravis patientsSubset of patientsMouse neuromuscular junctionHuman monoclonal autoantibodiesMuSK autoantibodiesAutoimmune mechanismsGravis patientsMG patientsMost patientsPathogenic autoantibodiesAutoimmune disordersMuscle weaknessNeuromuscular transmissionMuSK phosphorylationAutoantibodiesB cellsAcetylcholine receptorsSynaptic differentiationPatients
2018
Radiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab
Thomas A, Rosenblum M, Karimi S, DeAngelis LM, Omuro A, Kaley TJ. Radiographic patterns of recurrence and pathologic correlation in malignant gliomas treated with bevacizumab. CNS Oncology 2018, 07: 7-13. PMID: 29388793, PMCID: PMC6001559, DOI: 10.2217/cns-2017-0025.Peer-Reviewed Original ResearchConceptsMalignant gliomasRecurrence patternsDiffusion-weighted imaging abnormalitiesDiffusion-weighted imagingStandard clinical settingMG patientsImaging abnormalitiesMRI abnormalitiesPathologic findingsTumor recurrenceRadiographic patternsPathologic correlationBevacizumabClinical settingNecrosisPatientsRecurrenceRecent reportsTumorsGliomasAbnormalitiesLeptomeningealSurgery
2017
Autoantibody-producing plasmablasts after B cell depletion identified in muscle-specific kinase myasthenia gravis
Stathopoulos P, Kumar A, Nowak RJ, O’Connor K. Autoantibody-producing plasmablasts after B cell depletion identified in muscle-specific kinase myasthenia gravis. JCI Insight 2017, 2: e94263. PMID: 28878127, PMCID: PMC5621905, DOI: 10.1172/jci.insight.94263.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAnimalsAutoantibodiesB-LymphocytesCohort StudiesFemaleHumansImmunologic FactorsLymphocyte DepletionMaleMiceMiddle AgedMyasthenia GravisReceptor Protein-Tyrosine KinasesReceptors, CholinergicRecurrenceRemission InductionRituximabTumor Necrosis Factor Receptor Superfamily, Member 7ConceptsB-cell depletionMuSK-MG patientsMyasthenia gravisCell depletionMG patientsAutoantibody productionDisease relapseB cellsB-cell-mediated autoimmune disordersMuscle-specific kinase myasthenia gravisAntigen-driven affinity maturationCell-mediated autoimmune disordersMuscle-specific tyrosine kinaseAChR myasthenia gravisAutoantibody-producing plasmablastsMuSK myasthenia gravisRituximab-induced remissionSustained clinical improvementB cell compartmentMuSK autoantibodiesClinical improvementPathogenic autoantibodiesSuch relapsesSerum autoantibodiesClinical features
2016
Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production
Cao Y, Amezquita RA, Kleinstein SH, Stathopoulos P, Nowak RJ, O'Connor KC. Autoreactive T Cells from Patients with Myasthenia Gravis Are Characterized by Elevated IL-17, IFN-γ, and GM-CSF and Diminished IL-10 Production. The Journal Of Immunology 2016, 196: 2075-2084. PMID: 26826242, PMCID: PMC4761502, DOI: 10.4049/jimmunol.1501339.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAged, 80 and overAutoimmunityCD4-Positive T-LymphocytesCell SeparationCytokinesEnzyme-Linked Immunosorbent AssayFemaleGranulocyte-Macrophage Colony-Stimulating FactorHumansInterferon-gammaInterleukin-10Interleukin-17MaleMiddle AgedMyasthenia GravisPhenotypePolymerase Chain ReactionT-Lymphocyte SubsetsConceptsAutoreactive T cellsT cell compartmentHealthy control subjectsMyasthenia gravisT cellsMG patientsIL-17Control subjectsT cell librariesB cellsGM-CSFMemory T cell compartmentElevated IL-17Prototypical autoimmune diseaseIL-10 productionMemory T cellsCell compartmentIL-10 expressionB cell compartmentPathogenic phenotypeMG cohortPathogenic autoantibodiesAutoimmune responseClinical manifestationsProinflammatory phenotype
2012
Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma
Omuro A, Chan TA, Abrey LE, Khasraw M, Reiner AS, Kaley TJ, Deangelis LM, Lassman AB, Nolan CP, Gavrilovic IT, Hormigo A, Salvant C, Heguy A, Kaufman A, Huse JT, Panageas KS, Hottinger AF, Mellinghoff I. Phase II trial of continuous low-dose temozolomide for patients with recurrent malignant glioma. Neuro-Oncology 2012, 15: 242-250. PMID: 23243055, PMCID: PMC3548585, DOI: 10.1093/neuonc/nos295.Peer-Reviewed Original ResearchConceptsKarnofsky performance scoreProgression-free survival ratesBevacizumab-naive patientsRecurrent malignant gliomaPhase II trialMalignant gliomasII trialPrimary endpointSurvival rateContinuous low-dose temozolomideMedian Karnofsky performance scoreLow Karnofsky performance scoreAdvanced malignant gliomaLow-dose temozolomideMedian overall survivalHalf of patientsFurther treatment strategiesMutations of EGFRBevacizumab exposureEligible patientsTemozolomide schedulesMG patientsOverall survivalMedian ageClinical benefit
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