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
2023
Safety and Efficacy of Nipocalimab in Patients With Generalized Myasthenia Gravis
Antozzi C, Guptill J, Bril V, Gamez J, Meuth S, Nowak R, Quan D, Sevilla T, Jouvin M, Jin J, Karcher K, Ramchandren S, Sun H, Ling L, Zhu Y, Arroyo S, Group F. Safety and Efficacy of Nipocalimab in Patients With Generalized Myasthenia Gravis. Neurology 2023, 102: e207937. PMID: 38165333, PMCID: PMC10962909, DOI: 10.1212/wnl.0000000000207937.Peer-Reviewed Original ResearchMeSH KeywordsActivities of Daily LivingAntibodies, MonoclonalAutoantibodiesHumansMyasthenia GravisPatientsConceptsTreatment-emergent adverse eventsGeneralized myasthenia gravisSignificant dose responseAdverse eventsMG-ADLDay 57Myasthenia gravisDose responseMyasthenia Gravis ActivitiesPrimary safety endpointPrimary efficacy endpointSerious adverse eventsPhase 2 studyReceptor monoclonal antibodyDaily living (IADL) total scoreClinical trial registrationMG-ADL scoreDose-dependent reductionEudraCT numberQ2W groupEfficacy endpointPlacebo groupSafety endpointCare therapyReceptor autoantibodiesRemission 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 treatmentIndividual 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 conditionsMOGSerumRelapseCytotoxicityClinicoserological 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 ResearchMeSH KeywordsAutoantibodiesComplement ActivationHumansImmune Checkpoint InhibitorsMyasthenia GravisReceptors, Cholinergic
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 repertoire
2020
Clinical characteristics of fibroblast growth factor receptor 3 antibody‐related polyneuropathy: a retrospective study
Kovvuru S, Cardenas Y, Huttner A, Nowak R, Roy B. Clinical characteristics of fibroblast growth factor receptor 3 antibody‐related polyneuropathy: a retrospective study. European Journal Of Neurology 2020, 27: 1310-1318. PMID: 32068339, DOI: 10.1111/ene.14180.Peer-Reviewed Original ResearchConceptsChronic inflammatory neuropathiesInflammatory neuropathiesSensory neuropathyFGFR3 antibodiesDistal lower extremity weaknessIntravenous immunoglobulin responseLower extremity paresthesiasCommon presenting symptomLower extremity weaknessRetrospective chart reviewPure sensory neuropathyHistory of cancerDistal sensationMotor findingsPresenting symptomChart reviewClinical characteristicsDemyelinating featuresNerve biopsySymptom onsetUnsteady gaitClinical presentationFoot dropRetrospective studyAutoimmune diseases