2020
Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity
Xu J, Liu RJ, Fahey S, Frick L, Leckman J, Vaccarino F, Duman RS, Williams K, Swedo S, Pittenger C. Antibodies From Children With PANDAS Bind Specifically to Striatal Cholinergic Interneurons and Alter Their Activity. American Journal Of Psychiatry 2020, 178: 48-64. PMID: 32539528, PMCID: PMC8573771, DOI: 10.1176/appi.ajp.2020.19070698.Peer-Reviewed Original ResearchConceptsStriatal cholinergic interneuronsCholinergic interneuronsMouse brain slicesObsessive-compulsive disorderControl subjectsBrain slicesPediatric autoimmune neuropsychiatric disordersIntravenous immunoglobulin treatmentAutoimmune neuropsychiatric disordersAcute mouse brain slicesParvalbumin-expressing GABAergic interneuronsPediatric obsessive-compulsive disorderBrain antigensImmunoglobulin treatmentBaseline serumStreptococcal infectionCritical cellular targetsSymptom improvementGABAergic interneuronsInduced autoimmunityIgG antibodiesMouse slicesIndependent cohortBehavioral pathologyNeuron types
2013
Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease
Cox CJ, Sharma M, Leckman JF, Zuccolo J, Zuccolo A, Kovoor A, Swedo SE, Cunningham MW. Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease. The Journal Of Immunology 2013, 191: 5524-5541. PMID: 24184556, PMCID: PMC3848617, DOI: 10.4049/jimmunol.1102592.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, BacterialAutoantibodiesBasal GangliaChildChoreaCross ReactionsDopamineDopaminergic NeuronsG(M1) GangliosideHEK293 CellsHumansImmunoglobulin GMiceMice, Inbred C57BLMice, TransgenicReceptors, Dopamine D2Recombinant Fusion ProteinsRheumatic FeverSignal TransductionStreptococcal InfectionsTransgenesConceptsSydenham's choreaDopamine D2 receptorsDopaminergic neuronsD2 receptorsTransgenic micePediatric autoimmune neuropsychiatric disordersDose-dependent inhibitoryMain neurologic manifestationsAutoimmune neuropsychiatric disordersBehavioral disordersHuman monoclonal autoantibodiesBrain AgsNeurologic manifestationsRheumatic feverChoreiform movementsTg miceBasal gangliaHuman dopamine D2 receptorAb reactivityTyrosine hydroxylaseAutoantibodiesB cellsMonoclonal autoantibodiesNeuropsychiatric disordersD2R
2012
Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders
Brimberg L, Benhar I, Mascaro-Blanco A, Alvarez K, Lotan D, Winter C, Klein J, Moses AE, Somnier FE, Leckman JF, Swedo SE, Cunningham MW, Joel D. Behavioral, Pharmacological, and Immunological Abnormalities after Streptococcal Exposure: A Novel Rat Model of Sydenham Chorea and Related Neuropsychiatric Disorders. Neuropsychopharmacology 2012, 37: 2076-2087. PMID: 22534626, PMCID: PMC3398718, DOI: 10.1038/npp.2012.56.Peer-Reviewed Original ResearchConceptsSydenham's choreaNeuropsychiatric disordersStreptococcal exposureImmunological abnormalitiesMotor symptomsRat modelAnimal modelsSelective serotonin reuptake inhibitor paroxetineGroup A streptococcal infectionsSerotonin reuptake inhibitor paroxetineSK-N-SH neuronal cellsMale Lewis ratsNovel rat modelNew animal modelCalcium/calmodulin-dependent protein kinase IIRelated neuropsychiatric disordersStreptococcal infectionLewis ratsAntibody depositionBasal gangliaCalmodulin-dependent protein kinase IIDopamine D1GAS antigensGlutamate levelsD2 receptors
2009
Immunopathogenic mechanisms in tourette syndrome: A critical review
Martino D, Dale RC, Gilbert DL, Giovannoni G, Leckman JF. Immunopathogenic mechanisms in tourette syndrome: A critical review. Movement Disorders 2009, 24: 1267-1279. PMID: 19353683, PMCID: PMC3972005, DOI: 10.1002/mds.22504.Peer-Reviewed Original ResearchConceptsTourette syndromeT cellsTS patientsBeta-haemolytic streptococcal infectionPathogenesis of TSPeripheral immune cellsRegulatory T cellsCell-mediated mechanismsPro-inflammatory cytokinesCourse of diseaseGeneration of ticsAdaptive immune systemImmune effector moleculesAntineuronal antibodiesImmunopathogenic mechanismsLymphocyte subpopulationsNatural killerStreptococcal infectionAutoimmune responseImmune activationPlasma levelsDisease onsetImmune cellsPathogenic roleImmune response
2006
Identification of pyruvate kinase as an antigen associated with Tourette syndrome
Kansy JW, Katsovich L, McIver KS, Pick J, Zabriskie JB, Lombroso PJ, Leckman JF, Bibb JA. Identification of pyruvate kinase as an antigen associated with Tourette syndrome. Journal Of Neuroimmunology 2006, 181: 165-176. PMID: 17011640, PMCID: PMC1853370, DOI: 10.1016/j.jneuroim.2006.08.007.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAmino Acid SequenceAnimalsAntibodies, BacterialAntigensAutoantibodiesBrainChildCross ReactionsHumansImmunohistochemistryLongitudinal StudiesMaleMiceMice, Inbred C57BLMolecular Sequence DataProspective StudiesPyruvate KinaseRatsSeroepidemiologic StudiesStreptococcal InfectionsTicsTourette SyndromeConceptsStreptococcal infectionObsessive-compulsive disorderTourette syndromeAutoimmune targetExacerbated symptomsBeta-hemolytic streptococcal infectionEarly-onset obsessive-compulsive disorderStreptococcal M proteinPediatric populationTic disordersImmune responseSurface antigenInfectious strainsSyndromeInfectionDisordersPyruvate kinaseM proteinPatientsImmunoreactivitySymptomsAntigenAntibodiesGlycolytic enzymesM1 isoform
2005
Antineural antibody in patients with Tourette’s syndrome and their family members
Yeh CB, Wu CH, Tsung HC, Chen CW, Shyu JF, Leckman JF. Antineural antibody in patients with Tourette’s syndrome and their family members. Journal Of Biomedical Science 2005, 13: 101-112. PMID: 16215701, DOI: 10.1007/s11373-005-9033-y.Peer-Reviewed Original ResearchConceptsAntineural antibodiesTourette syndromeTS patientsTic disordersControl groupFirst-degree family membersAge-matched control groupFamily membersSera of controlsImmunological pathophysiologyStreptococcal infectionPrimary cell culturesPatientsInfectious agentsSyndromeNeuropsychiatric disordersWestern blottingAntibodiesRat tissuesInteraction of geneticsGenetic vulnerabilitySerumDisordersFuture studiesCell culturesMicroinfusion of antineuronal antibodies into rodent striatum: Failure to differentiate between elevated and low titers
Singer HS, Mink JW, Loiselle CR, Burke KA, Ruchkina I, Morshed S, Parveen S, Leckman JF, Hallett JJ, Lombroso PJ. Microinfusion of antineuronal antibodies into rodent striatum: Failure to differentiate between elevated and low titers. Journal Of Neuroimmunology 2005, 163: 8-14. PMID: 15885303, DOI: 10.1016/j.jneuroim.2005.02.018.Peer-Reviewed Original ResearchConceptsAntineuronal antibodiesMovement disordersMale Sprague-Dawley ratsPediatric movement disordersSerum antineuronal antibodiesSprague-Dawley ratsStart of infusionNonspecific behavioral effectsAttention deficit hyperactivity disorderDeficit hyperactivity disorderAntibody infusionSham surgeryVentrolateral striatumObsessive-compulsive disorderSerum titersAntibody titersUse of ELISAImmunohistochemical techniquesTourette syndromeBehavioral abnormalitiesRodent striatumDay 2Stereotypy scoresInfusionLow titers
2002
An Animal Model of Tourettes Syndrome
Taylor JR, Morshed SA, Parveen S, Mercadante MT, Scahill L, Peterson BS, King RA, Leckman JF, Lombroso PJ. An Animal Model of Tourettes Syndrome. American Journal Of Psychiatry 2002, 159: 657-660. PMID: 11925307, DOI: 10.1176/appi.ajp.159.4.657.Peer-Reviewed Original Research