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 assaysMAbsPatients
2020
Affinity maturation is required for pathogenic monovalent IgG4 autoantibody development in myasthenia gravis
Fichtner ML, Vieni C, Redler RL, Kolich L, Jiang R, Takata K, Stathopoulos P, Suarez PA, Nowak RJ, Burden SJ, Ekiert DC, O’Connor K. Affinity maturation is required for pathogenic monovalent IgG4 autoantibody development in myasthenia gravis. Journal Of Experimental Medicine 2020, 217: e20200513. PMID: 32820331, PMCID: PMC7953735, DOI: 10.1084/jem.20200513.Peer-Reviewed Original ResearchConceptsMyasthenia gravisUnmutated common ancestorPathogenic capacityMuscle-specific tyrosine kinaseAffinity maturationMuSK myasthenia gravisAutoimmune myasthenia gravisMonovalent antigen-binding fragmentsUnique autoantibodiesIgG4 autoantibodiesAutoantibody developmentAutoantibodiesFab-arm exchangeMonoclonal autoantibodiesAntigen-binding fragmentsGravisSomatic mutationsSubnanomolar affinityMAbsMonovalent FabTyrosine kinaseMaturationImmunopathologyAutoimmunityMonovalent IgG4 autoantibodies require self-antigen driven affinity maturation to acquire pathogenic capacity
Fichtner M, Vieni C, Redler R, Jiang R, Suarez P, Nowak R, Burden S, Bhabha G, Ekiert D, O’Connor K. Monovalent IgG4 autoantibodies require self-antigen driven affinity maturation to acquire pathogenic capacity. The Journal Of Immunology 2020, 204: 224.39-224.39. DOI: 10.4049/jimmunol.204.supp.224.39.Peer-Reviewed Original ResearchMuSK myasthenia gravisMyasthenia gravisUnmutated common ancestorPathogenic capacityB-cell-mediated autoimmune diseasesAntigen-driven affinity maturationCell-mediated autoimmune diseaseMuscle-specific tyrosine kinaseSubset of patientsAutoreactive B cellsMonovalent antigen-binding fragmentsAffinity maturationHuman monoclonal autoantibodiesUnique autoantibodiesIgG4 autoantibodiesPathogenic autoantibodiesAutoimmune disordersAutoimmune responseAutoimmune diseasesSelf antigensIgG4 subclassAutoantibodiesMG autoantibodiesB cellsFab-arm exchange