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 ResearchConceptsTreatment-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 treatmentLeg MRI as a Complementary Diagnostic Tool in the Assessment of Foot Drop
Torabi T, Zubair A, Nowak R, Tseng B, Haims A, Roy B. Leg MRI as a Complementary Diagnostic Tool in the Assessment of Foot Drop. Journal Of Clinical Neuromuscular Disease 2023, 25: 57-58. PMID: 37611274, DOI: 10.1097/cnd.0000000000000433.Peer-Reviewed Original ResearchPlasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions
Zubair A, Rethana M, Ma A, McAlpine L, Abulaban A, Munro B, Patwa H, Nowak R, Roy B. Plasmapheresis Versus Intravenous Immunoglobulin in Patients With Autoimmune Neuromuscular and Neuro-immunological Conditions. Journal Of Clinical Neuromuscular Disease 2023, 25: 11-17. PMID: 37611265, DOI: 10.1097/cnd.0000000000000439.Peer-Reviewed Original ResearchConceptsNeuro-immunological diseaseIntravenous immunoglobulinAutoimmune neurological disordersAutoimmune neuromuscular disorderAdult patientsElderly patientsNeurological disordersNeuromuscular disordersChronic inflammatory demyelinating polyradiculoneuropathyNational Inpatient Sample databaseNational Inpatient Sample datasetInflammatory demyelinating polyradiculoneuropathySafe therapeutic choiceRetrospective chart reviewAppropriate clinical settingSide effect profileDemyelinating polyradiculoneuropathyIVIG useChart reviewYounger patientsMyasthenia gravisEffect profileMedical historyPrimary diagnosisTherapeutic choiceIndividual 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 muscleDermatomyositisPolymyositisMyositisAddressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials
Guptill J, Benatar M, Granit V, Habib A, Howard J, Barnett-Tapia C, Nowak R, Lee I, Ruzhansky K, Dimachkie M, Cutter G, Kaminski H, Group F. Addressing Outcome Measure Variability in Myasthenia Gravis Clinical Trials. Neurology 2023, 101: 442-451. PMID: 37076302, PMCID: PMC10491448, DOI: 10.1212/wnl.0000000000207278.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 Research
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
Reply to: What is the pattern of the neuropathy associated with anti‐FGFR3 antibodies?
Roy B, Kovvuru S, Castillo Y, Huttner A, Nowak R. Reply to: What is the pattern of the neuropathy associated with anti‐FGFR3 antibodies? European Journal Of Neurology 2020, 27: e59-e59. PMID: 32503081, DOI: 10.1111/ene.14381.Peer-Reviewed Original ResearchClinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis
Howard JF, Nowak RJ, Wolfe GI, Freimer ML, Vu TH, Hinton JL, Benatar M, Duda PW, MacDougall JE, Farzaneh-Far R, Kaminski HJ, Barohn R, Dimachkie M, Pasnoor M, Farmakidis C, Liu T, Colgan S, Benatar M, Bertorini T, Pillai R, Henegar R, Bromberg M, Gibson S, Janecki T, Freimer M, Elsheikh B, Matisak P, Genge A, Guidon A, David W, Habib A, Mathew V, Mozaffar T, Hinton J, Hewitt W, Barnett D, Sullivan P, Ho D, Howard J, Traub R, Chopra M, Kaminski H, Aly R, Bayat E, Abu-Rub M, Khan S, Lange D, Holzberg S, Khatri B, Lindman E, Olapo T, Sershon L, Lisak R, Bernitsas E, Jia K, Malik R, Lewis-Collins T, Nicolle M, Nowak R, Sharma A, Roy B, Nye J, Pulley M, Berger A, Shabbir Y, Sachdev A, Patterson K, Siddiqi Z, Sivak M, Bratton J, Small G, Kohli A, Fetter M, Vu T, Lam L, Harvey B, Wolfe G, Silvestri N, Patrick K, Zakalik K, Duda P, MacDougall J, Farzaneh-Far R, Pontius A, Hoarty M. Clinical Effects of the Self-administered Subcutaneous Complement Inhibitor Zilucoplan in Patients With Moderate to Severe Generalized Myasthenia Gravis. JAMA Neurology 2020, 77: 582-592. PMID: 32065623, PMCID: PMC7042797, DOI: 10.1001/jamaneurol.2019.5125.Peer-Reviewed Original ResearchConceptsGeneralized myasthenia gravisSecondary end pointsDaily living scoreTolerability profileEnd pointLiving scoreMyasthenia gravisClinical effectsPlacebo-controlled phase 2 clinical trialKey secondary efficacy end pointsKey secondary end pointSecondary efficacy end pointsSevere Generalized Myasthenia GravisQuantitative Myasthenia Gravis ScorePhase 2 clinical trialAcetylcholine receptor autoantibodiesEfficacy end pointMyasthenia gravis scoreMG activityComplement component 5Disease-specific variablesQuality of lifeComplete complement inhibitionBroader populationDaily SCGuidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic
Group I, Jacob S, Muppidi S, Guidon A, Guptill J, Hehir M, Howard J, Illa I, Mantegazza R, Murai H, Utsugisawa K, Vissing J, Wiendl H, Nowak R. Guidance for the management of myasthenia gravis (MG) and Lambert-Eaton myasthenic syndrome (LEMS) during the COVID-19 pandemic. Journal Of The Neurological Sciences 2020, 412: 116803. PMID: 32247193, PMCID: PMC7105910, DOI: 10.1016/j.jns.2020.116803.Peer-Reviewed Original ResearchMeSH KeywordsBetacoronavirusClinical Trials as TopicCoronavirus InfectionsCOVID-19COVID-19 Drug TreatmentDisease ManagementDisease SusceptibilityHumansImmunoglobulins, IntravenousImmunologic FactorsImmunosuppressive AgentsImmunotherapyLambert-Eaton Myasthenic SyndromeMyasthenia GravisPandemicsPlasma ExchangePneumonia, ViralSARS-CoV-2VaccinesClinical 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
2015
Editorial by concerned physicians: Unintended effect of the orphan drug act on the potential cost of 3,4‐diaminopyridine
Burns TM, Smith GA, Allen JA, Amato AA, Arnold WD, Barohn R, Benatar M, Bird SJ, Bromberg M, Chahin N, Ciafaloni E, Cohen JA, Corse A, Crum BA, David WS, Dimberg E, Sousa E, Donofrio PD, Dyck PJ, Engel AG, Ensrud ER, Ferrante M, Freimer M, Gable KL, Gibson S, Gilchrist JM, Goldstein JM, Gooch CL, Goodman BP, Gorelov D, Gospe SM, Goyal NA, Guidon AC, Guptill JT, Gutmann L, Gutmann L, Gwathmey K, Harati Y, Harper CM, Hehir MK, Hobson-Webb L, Howard JF, Jackson CE, Johnson N, Jones SM, Juel VC, Kaminski HJ, Karam C, Kennelly KD, Khella S, Khoury J, Kincaid JC, Kissel JT, Kolb N, Lacomis D, Ladha S, Larriviere D, Lewis RA, Li Y, Litchy WJ, Logigian E, Lou J, MacGowen DJ, Maselli R, Massey JM, Mauermann ML, Mathews KD, Meriggioli MN, Miller RG, Moon J, Mozaffar T, Nations SP, Nowak RJ, Ostrow LW, Pascuzzi RM, Peltier A, Ruzhansky K, Richman DP, Ross MA, Rubin DI, Russell JA, Sachs GM, Salajegheh MK, Saperstein DS, Scelsa S, Selcen D, Shaibani A, Shieh PB, Silvestri NJ, Singleton JR, Smith BE, So YT, Solorzano G, Sorenson EJ, Srinivasen J, Tavee J, Tawil R, Thaisetthawatkul P, Thornton C, Trivedi J, Vernino S, Wang AK, Webb TA, Weiss MD, Windebank AJ, Wolfe GI. Editorial by concerned physicians: Unintended effect of the orphan drug act on the potential cost of 3,4‐diaminopyridine. Muscle & Nerve 2015, 53: 165-168. PMID: 26662952, DOI: 10.1002/mus.25009.Peer-Reviewed Original Research
2004
An Intersubunit Disulfide Bond Prevents in Vitro Aggregation of a Superoxide Dismutase-1 Mutant Linked to Familial Amytrophic Lateral Sclerosis †
Ray SS, Nowak RJ, Strokovich K, Brown RH, Walz T, Lansbury PT. An Intersubunit Disulfide Bond Prevents in Vitro Aggregation of a Superoxide Dismutase-1 Mutant Linked to Familial Amytrophic Lateral Sclerosis †. Biochemistry 2004, 43: 4899-4905. PMID: 15109247, DOI: 10.1021/bi030246r.Peer-Reviewed Original ResearchConceptsSuperoxide dismutase 1Familial amyotrophic lateral sclerosisDisulfide bondsDisease-associated proteinsIntersubunit disulfide bondsWild-type SOD1Symmetry-related residuesWild-type superoxide dismutase 1Dimer interfaceMutant formsAmyloid poresMutant superoxide dismutase 1Pathogenic speciesAmytrophic lateral sclerosisAbolished aggregationConcentration-dependent lossSOD1 inclusionsVitro aggregationPoint mutationsDimer dissociationEnzymatic activityWT dimerLateral sclerosisDismutase 1Animal modeling studies
2002
α-Synuclein, Especially the Parkinson's Disease-associated Mutants, Forms Pore-like Annular and Tubular Protofibrils
Lashuel HA, Petre BM, Wall J, Simon M, Nowak RJ, Walz T, Lansbury PT. α-Synuclein, Especially the Parkinson's Disease-associated Mutants, Forms Pore-like Annular and Tubular Protofibrils. Journal Of Molecular Biology 2002, 322: 1089-1102. PMID: 12367530, DOI: 10.1016/s0022-2836(02)00735-0.Peer-Reviewed Original Research