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 kinaseMaturationImmunopathologyAutoimmunity
2015
Imaging robust microglial activation after lipopolysaccharide administration in humans with PET
Sandiego CM, Gallezot JD, Pittman B, Nabulsi N, Lim K, Lin SF, Matuskey D, Lee JY, O’Connor K, Huang Y, Carson RE, Hannestad J, Cosgrove KP. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 12468-12473. PMID: 26385967, PMCID: PMC4603509, DOI: 10.1073/pnas.1511003112.Peer-Reviewed Original ResearchConceptsMicroglial activationBrain microglial activationLPS administrationInflammatory cytokinesLPS challengeRobust microglial activationSystemic LPS challengeActivation of microgliaInnate immune cellsVital sign changesHealthy male subjectsEscherichia coli lipopolysaccharidePositron emission tomography (PET) radiotracerNeuroinflammatory responseSystemic inflammationLipopolysaccharide administrationAntiinflammatory effectsBlood levelsImmune cellsNew medicationsSystemic administrationColi lipopolysaccharidePET scansPsychiatric diseasesMale subjects
2013
The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study
Hannestad J, DellaGioia N, Gallezot JD, Lim K, Nabulsi N, Esterlis I, Pittman B, Lee JY, O’Connor K, Pelletier D, Carson RE. The neuroinflammation marker translocator protein is not elevated in individuals with mild-to-moderate depression: A [11C]PBR28 PET study. Brain Behavior And Immunity 2013, 33: 131-138. PMID: 23850810, PMCID: PMC3899398, DOI: 10.1016/j.bbi.2013.06.010.Peer-Reviewed Original ResearchConceptsLevels of TSPOControl subjectsSystemic inflammationPositron emission tomographyModerate depressionTSPO levelsActivation of microgliaTranslocator protein 18Total ligand bindingAcute episodePrimary outcomePostmortem studiesSevere depressionMajor depressionPET scansTSPO genotypeBrain regionsEmission tomographySubject factorsPET studiesArterial input functionInflammationElevated levelsProtein 18Depression
2012
Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis
Ray A, Amato AA, Bradshaw EM, Felice KJ, DiCapua DB, Goldstein JM, Lundberg IE, Nowak RJ, Ploegh HL, Spooner E, Wu Q, Willis SN, O’Connor K. Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis. PLOS ONE 2012, 7: e46709. PMID: 23071619, PMCID: PMC3465259, DOI: 10.1371/journal.pone.0046709.Peer-Reviewed Original ResearchConceptsInclusion body myositisHumoral immune responseImmune responsePlasma cellsTissue damageBody myositisAntibody-secreting plasma cellsCell linesSingle plasma cellsMajor intermediate filament proteinMuscle tissueIBM patientsHumoral autoimmunityInflammatory myopathiesHuman-derived cell linesIBM muscleMuscle tissue sectionsMuscle tissue homogenatesMuscle diseaseTissue homogenatesTissue sectionsIntermediate filament proteinsMyositisAutoantibodiesDisease
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