2024
Fluorescence-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 chromatographyPatientsReceptors
2023
Individual 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 assaysMAbsPatientsClinicoserological 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 repertoireMyasthenia gravis complement activity is independent of autoantibody titer and disease severity
Fichtner ML, Hoarty MD, Vadysirisack DD, Munro-Sheldon B, Nowak RJ, O’Connor K. Myasthenia gravis complement activity is independent of autoantibody titer and disease severity. PLOS ONE 2022, 17: e0264489. PMID: 35290370, PMCID: PMC8923450, DOI: 10.1371/journal.pone.0264489.Peer-Reviewed Original ResearchConceptsAutoantibody titersComplement activityDisease activityMyasthenia gravisComplement pathwayAcetylcholine receptor autoantibodiesAutoimmune myasthenia gravisSecondary complement deficiencyClassical complement pathwayAChR autoantibodiesReceptor autoantibodiesClinical statusAutoimmune diseasesHealthy controlsComplement deficiencyPatients associatesStudy subjectsCandidate biomarkersDisease statusDisease severitySignificant associationDisease pathologyTitersAutoantibodiesPatients
2020
The B cell immunobiology that underlies CNS autoantibody-mediated diseases
Sun B, Ramberger M, O’Connor K, Bashford-Rogers RJM, Irani SR. The B cell immunobiology that underlies CNS autoantibody-mediated diseases. Nature Reviews Neurology 2020, 16: 481-492. PMID: 32724223, PMCID: PMC9364389, DOI: 10.1038/s41582-020-0381-z.Peer-Reviewed Original ResearchConceptsAutoantigen-specific B cellsB cellsPathogenic autoantibodiesB cell tolerance checkpointsAutoantibody-mediated diseasesB cell immunobiologyLong-term morbidityHigher serum levelsCirculation of patientsSource of autoantibodiesSite of pathologyB-cell lineageClinical relapseAvailable medicationsSerum levelsIntrathecal synthesisCNS diseaseTolerance checkpointsPlasma cellsTherapeutic effectCerebrospinal fluidGerminal centersAutoantibodiesDiseasePatients
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
2017
The Inclusion Body Myositis Registry at Yale: A growing information database and practical tool for researchers, clinicians, and patients
Cotzomi E, Petschke K, O'Connor K, Paltiel A. The Inclusion Body Myositis Registry at Yale: A growing information database and practical tool for researchers, clinicians, and patients. Muscle & Nerve 2017 DOI: 10.1002/mus.25774.Peer-Reviewed Original Research
2016
Restoring immune tolerance in neuromyelitis optica
Steinman L, Bar-Or A, Behne J, Benitez-Ribas D, Chin P, Clare-Salzler M, Healey D, Kim J, Kranz D, Lutterotti A, Martin R, Schippling S, Villoslada P, Wei C, Weiner H, Zamvil S, Yeaman M, Smith T, Consortium G, Aktas O, Amezcua L, Appiwatanakul M, Asgari N, Banwell B, Bennett J, Bowen J, Cabre P, Chitnis T, Cohen J, De Seze J, Fujihara K, Han M, Hellwig K, Hintzen R, Hooper D, Iorio R, Jacob A, Jarius S, Kim H, Kissani N, Klawiter E, Kleiter I, Lana-Peixoto M, Leite M, Levy M, Lublin F, Draayer Y, Marignier R, Matiello M, Nakashima I, O’Connor K, Palace J, Pandit L, Paul F, Prayoonwiwat N, Riley C, Ruprecht K, Saiz A, Siritho S, Tenembaum S, Weinshenker B, Wingerchuk D, Würfel J. Restoring immune tolerance in neuromyelitis optica. Neurology Neuroimmunology & Neuroinflammation 2016, 3: &na;. PMID: 27648463, PMCID: PMC5015539, DOI: 10.1212/nxi.0000000000000276.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsNMO/SDNeuromyelitis opticaImmune toleranceAquaporin-4 (AQP4) water channel proteinKey immune mechanismsImmune tolerizationDevelopment of cancerEmpirical therapyOptic nerveRandomized trialsImmunologic suppressionAutoimmune diseasesSerious infectionsAstrocyte dysfunctionCurrent therapiesImmune mechanismsSpinal cordClinical variantsDominant autoantigenAquaporin-4Therapeutic restorationRestorative techniquesTherapyOpticaPatients
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 individuals
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
A 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
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