2024
Author Correction: Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells
Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi E, Alvarado A, Cottman-Thomas E, Maseda D, Tsao P, Ellebrecht C, Khella S, Richman D, O’Connor K, Herzberg U, Binder G, Milone M, Basu S, Payne A. Author Correction: Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nature Biotechnology 2024, 1-1. PMID: 39543316, DOI: 10.1038/s41587-024-02502-x.Peer-Reviewed Original ResearchFluorescence-detection size-exclusion chromatography specifically detects autoantibodies targeting the ganglionic acetylcholine receptor in patients with autoimmune autonomic ganglionopathy
Baxter L, Hopkins S, O'Connor K, Pham M, Nowak R, Monson N, Blackburn K, Hibbs R, Vernino S, Noviello C. Fluorescence-detection size-exclusion chromatography specifically detects autoantibodies targeting the ganglionic acetylcholine receptor in patients with autoimmune autonomic ganglionopathy. Journal Of Neuroimmunology 2024, 396: 578454. PMID: 39277987, DOI: 10.1016/j.jneuroim.2024.578454.Peer-Reviewed Original ResearchAutoimmune autonomic ganglionopathyGanglionic acetylcholine receptorAutonomic ganglionopathyRadioimmunoprecipitation assayFluorescence-detection size-exclusion chromatographyAcetylcholine receptorsAutoantibody detectionClinical symptomsDetect autoantibodiesAutoimmune diseasesHealthy controlsPatient seraSize-exclusion-chromatographyAutoantibodiesGAChRGanglionopathySize exclusion chromatographyPatientsReceptorsB cell and aquaporin‐4 antibody relationships with neuromyelitis optica spectrum disorder activity
Bennett J, Pittock S, Paul F, Kim H, Irani S, O'Connor K, Patterson K, Smith M, Gunsior M, Mittereder N, Rees W, Cimbora D, Cree B. B cell and aquaporin‐4 antibody relationships with neuromyelitis optica spectrum disorder activity. Annals Of Clinical And Translational Neurology 2024, 11: 2792-2798. PMID: 39222408, PMCID: PMC11514900, DOI: 10.1002/acn3.52171.Peer-Reviewed Original ResearchNeuromyelitis optica spectrum disorderAquaporin-4B cellsAquaporin-4 immunoglobulin GCirculating B cell subsetsAQP4-IgG titerN-MOmentum studyB-cell countsB cell subsetsBaseline to timePost hoc analysisInebilizumab treatmentAQP4-IgGCD20<sup>+</sup>Subset countsGene signatureHoc analysisInebilizumabNo differenceImmunoglobulin GNeuromyelitisBaselineDisordered activityTitersSpectrum disorderUnveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity
Bodansky A, Yu D, Rallistan A, Kalaycioglu M, Boonyaratanakornkit J, Green D, Gauthier J, Turtle C, Zorn K, O'Donovan B, Mandel-Brehm C, Asaki J, Kortbawi H, Kung A, Rackaityte E, Wang C, Saxena A, de Dios K, Masi G, Nowak R, O'Connor K, Li H, Diaz V, Saloner R, Casaletto K, Gontrum E, Chan B, Kramer J, Wilson M, Utz P, Hill J, Jackson S, Anderson M, DeRisi J. Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity. Journal Of Clinical Investigation 2024, 134: e180012. PMID: 38753445, PMCID: PMC11213466, DOI: 10.1172/jci180012.Peer-Reviewed Original ResearchB-cell maturation antigenImmunomodulatory therapyPlasma cell-targeted therapyCAR-T therapyCell-targeted therapyAutoantibody mediated diseasesCAR-TAnti-CD19Maturation antigenAutoantibody profileAutoreactive antibodiesTargeted therapyPlasma cellsAutoimmune diseasesAutoantibody repertoireTherapyMediated diseasesAutoantibodiesTherapeutic interventionsProteome-wideDisease statesDiseaseImmunological fingerprintPhIP-SeqMinimal effectProteomic Analysis Reveals a Distinct Immunological Signature for Late-onset Myasthenia Gravis (S15.003)
Roy B, Habiabadi F, O’Connor K, Nowak R, Kaminski H. Proteomic Analysis Reveals a Distinct Immunological Signature for Late-onset Myasthenia Gravis (S15.003). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000205944.Peer-Reviewed Original ResearchPhenotypes of B Cells Producing Autoantibodies in MOGAD Patients (N1.002)
Filipek B, Yandamuri S, Obaid A, Thurman J, Makhani N, Nowak R, Guo Y, Lucchinetti C, Flanagan E, Longbrake E, O’Connor K. Phenotypes of B Cells Producing Autoantibodies in MOGAD Patients (N1.002). Neurology 2024, 102 DOI: 10.1212/wnl.0000000000208259.Peer-Reviewed Original ResearchA 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
2023
From drab to Fab; PLP1's fit is redressed for MS.
Bayer A, O'Connor K. From drab to Fab; PLP1's fit is redressed for MS. Science Immunology 2023, 8: eadl0618. PMID: 37801515, DOI: 10.1126/sciimmunol.adl0618.Commentaries, Editorials and LettersRemission of severe myasthenia gravis after autologous stem cell transplantation
Schlatter M, Yandamuri S, O'Connor K, Nowak R, Pham M, Obaid A, Redman C, Provost M, McSweeney P, Pearlman M, Tees M, Bowen J, Nash R, Georges G. Remission of severe myasthenia gravis after autologous stem cell transplantation. Annals Of Clinical And Translational Neurology 2023, 10: 2105-2113. PMID: 37726935, PMCID: PMC10646993, DOI: 10.1002/acn3.51898.Peer-Reviewed Original ResearchConceptsHematopoietic cell transplantationRefractory myasthenia gravisAutologous hematopoietic cell transplantationMyasthenia gravisCell transplantationAcetylcholine receptorsAutologous stem cell transplantationPhase 2 clinical trialAmerica (MGFA) clinical classificationMultiple immunomodulatory agentsRabbit antithymocyte globulinSevere myasthenia gravisAutoimmune neurological disordersHigh-dose chemotherapyMyasthenia Gravis FoundationNeuromuscular junction disordersStem cell transplantationTherapeutic plasma exchangeImmune cell subtypesDays of treatmentEffect of treatmentAntithymocyte globulinDisease activityComplete responseUnderwent treatmentToddler's T cells are taught in muco-school.
Khani-Habibabadi F, O'Connor K. Toddler's T cells are taught in muco-school. Science Immunology 2023, 8: eadj9555. PMID: 37540737, DOI: 10.1126/sciimmunol.adj9555.Peer-Reviewed Original ResearchIndividual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology
Pham M, Masi G, Patzina R, Obaid A, Oxendine S, Oh S, Payne A, Nowak R, O’Connor K. Individual myasthenia gravis autoantibody clones can efficiently mediate multiple mechanisms of pathology. Acta Neuropathologica 2023, 146: 319-336. PMID: 37344701, PMCID: PMC11380498, DOI: 10.1007/s00401-023-02603-y.Peer-Reviewed Original ResearchConceptsMyasthenia gravisAntigenic modulationPathogenic mechanismsAutoimmune myasthenia gravisCurrent therapeutic approachesΑ-bungarotoxin bindingNicotinic acetylcholine receptorsReceptor blockadeSerum autoantibodiesAutoreactive clonesMonoclonal levelTherapeutic approachesMonoclonal autoantibodiesAcetylcholine receptorsComplement activationAutoantibodiesAChR subunitsJurkat cell lineDistinct molecular mechanismsPathogenic profilePathogenic capacityPathologyCell-based assaysMAbsPatientsMOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity
Yandamuri S, Filipek B, Obaid A, Lele N, Thurman J, Makhani N, Nowak R, Guo Y, Lucchinetti C, Flanagan E, Longbrake E, O’Connor K. MOGAD patient autoantibodies induce complement, phagocytosis, and cellular cytotoxicity. JCI Insight 2023, 8: e165373. PMID: 37097758, PMCID: PMC10393237, DOI: 10.1172/jci.insight.165373.Peer-Reviewed Original ResearchConceptsMyelin oligodendrocyte glycoprotein antibody-associated diseaseAntibody-dependent cellular phagocytosisAntibody-dependent cellular cytotoxicityComplement-dependent cytotoxicityMOG autoantibodiesPatient seraCellular cytotoxicityEffector functionsComplement activityAntibody-associated diseaseMultiple mechanismsNK cellsPatient autoantibodiesCytotoxic capacityLesion histologyCellular phagocytosisFuture relapseIgG subclassesCerebrospinal fluidAutoantibodiesCNS conditionsMOGSerumRelapseCytotoxicityThe Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties
Jiang R, Roy B, Wu Q, Mohanty S, Nowak R, Shaw A, Kleinstein S, O’Connor K. The Plasma Cell Infiltrate Populating the Muscle Tissue of Patients with Inclusion Body Myositis Features Distinct B Cell Receptor Repertoire Properties. ImmunoHorizons 2023, 7: 310-322. PMID: 37171806, PMCID: PMC10579972, DOI: 10.4049/immunohorizons.2200078.Peer-Reviewed Original ResearchConceptsInclusion body myositisMemory B cellsCell infiltrateBody myositisB cellsIBM muscle biopsiesB-cell infiltratesPlasma cell infiltrateClass-switched IgGMuscle tissueAdaptive immune receptor repertoire sequencingHumoral responseHealthy controlsIgA isotypePlasma cellsCell repertoireMuscle biopsyInfiltratesDegenerative disordersDisease pathologyRepertoire sequencingSkeletal muscleDermatomyositisPolymyositisMyositisInvestigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005)
Masi G, Pham M, Dai Y, Li Y, Karatz T, Oxendine S, Juel V, Ring A, Nowak R, Guptill J, O’Connor K. Investigating Autoantibody Profiles in Seronegative Myasthenia Gravis (P1-5.005). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000202639.Peer-Reviewed Original ResearchEarly B cell tolerance defects in anti-neurofascin 155 mediated chronic inflammatory demyelinating polyneuropathy (S40.005)
Roy B, Obaid A, Ohashi S, Coppola C, Das S, Hernandez A, Masi G, Martin-Aguilar L, Lleixà M, Nowak R, Querol Gutierrez L, O’Connor K. Early B cell tolerance defects in anti-neurofascin 155 mediated chronic inflammatory demyelinating polyneuropathy (S40.005). Neurology 2023, 100 DOI: 10.1212/wnl.0000000000203364.Peer-Reviewed Original ResearchClinicoserological insights into patients with immune checkpoint inhibitor‐induced myasthenia gravis
Masi G, Pham M, Karatz T, Oh S, Payne A, Nowak R, Howard J, Guptill J, Juel V, O'Connor K. Clinicoserological insights into patients with immune checkpoint inhibitor‐induced myasthenia gravis. Annals Of Clinical And Translational Neurology 2023, 10: 825-831. PMID: 36924454, PMCID: PMC10187728, DOI: 10.1002/acn3.51761.Peer-Reviewed Original ResearchPlasmablasts from the past: Nostalgic B cells can't let go.
Ohashi S, O'Connor K. Plasmablasts from the past: Nostalgic B cells can't let go. Science Immunology 2023, 8: eadh3115. PMID: 36867677, DOI: 10.1126/sciimmunol.adh3115.Peer-Reviewed Original ResearchPrecision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells
Oh S, Mao X, Manfredo-Vieira S, Lee J, Patel D, Choi E, Alvarado A, Cottman-Thomas E, Maseda D, Tsao P, Ellebrecht C, Khella S, Richman D, O’Connor K, Herzberg U, Binder G, Milone M, Basu S, Payne A. Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells. Nature Biotechnology 2023, 41: 1229-1238. PMID: 36658341, PMCID: PMC10354218, DOI: 10.1038/s41587-022-01637-z.Peer-Reviewed Original ResearchConceptsMuscle‐specific tyrosine kinase myasthenia gravisReceptor T cellsB cellsT cellsMyasthenia gravisChimeric autoantibody receptor T cellsCD19 chimeric antigen receptor T cellsAutoantigen-specific B cellsChimeric antigen receptor T cellsAntigen receptor T cellsAnti-MuSK antibodiesB-cell depletionTotal IgG levelsClinical study designInvestigational new drug applicationChronic immunosuppressionIgG levelsMuscle weaknessAutoimmune diseasesCell depletionCurrent therapiesSimilar efficacyCytolytic activityMouse modelNew drug applications
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 assays