2025
A lupus-derived autoantibody that binds to intracellular RNA activates cGAS-mediated tumor immunity and can deliver RNA into cells
Chen X, Tang X, Xie Y, Cuffari B, Tang C, Cao F, Gao X, Meng Z, Noble P, Young M, Turk O, Shirali A, Gera J, Nishimura R, Zhou J, Hansen J. A lupus-derived autoantibody that binds to intracellular RNA activates cGAS-mediated tumor immunity and can deliver RNA into cells. Science Signaling 2025, 18: eadk3320. PMID: 40132052, PMCID: PMC12076517, DOI: 10.1126/scisignal.adk3320.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusOrthotopic models of glioblastomaNecrotic tumor cellsPathophysiology of autoimmunityNonviral gene deliveryModels of glioblastomaTumor immunityOrthotopic modelT cellsLupus erythematosusTumor cellsGene deliveryAnimal survivalCyclic GMP-AMP synthaseImmune responseAutoantibodiesTherapeutic opportunitiesCancer treatmentPromote animal survivalDeliver RNAImmune signalingLiving miceAntibodiesCellsMuscle tissue
2024
Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition
Rackear M, Quijano E, Ianniello Z, Colón-Ríos D, Krysztofiak A, Abdullah R, Liu Y, Rogers F, Ludwig D, Dwivedi R, Bleichert F, Glazer P. Next-generation cell-penetrating antibodies for tumor targeting and RAD51 inhibition. Oncotarget 2024, 15: 699-713. PMID: 39352803, PMCID: PMC11444335, DOI: 10.18632/oncotarget.28651.Peer-Reviewed Original ResearchConceptsTumor targetingMonoclonal antibody therapyTumor-specific targetingCell uptakeNucleic acid bindingCell surface antigensAntibody therapyHuman variantsClinical successCell-penetrating antibodiesAcid bindingSystemic administrationSurface antigensTumorRAD51 inhibitionAntibody platformMechanism of cell penetrationBind RAD51AntibodiesFull-lengthSpecific targetsCell penetrationDisease targetsCellsAutoantibodiesFluorescence-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 chromatographyPatientsReceptorsCheckpoint Inhibitor-Induced Autoimmune Diabetes: An Autoinflammatory Disease.
Quandt Z, Perdigoto A, Anderson M, Herold K. Checkpoint Inhibitor-Induced Autoimmune Diabetes: An Autoinflammatory Disease. Cold Spring Harbor Perspectives In Medicine 2024, 15: a041603. PMID: 39038853, PMCID: PMC11917379, DOI: 10.1101/cshperspect.a041603.Peer-Reviewed Original ResearchAutoimmune diabetesBlockade of programmed cell death protein 1Agents targeting immune checkpointsCell death protein 1Autoimmune side effectsPD-L1Immune checkpointsAutoimmune disease riskClinical findingsAdverse eventsLevels of lipaseSide effectsInflammatory processIslets of LangerhansProtein 1DiabetesDisease riskIncreased levelsCheckpointAutoantibodiesBlockadeCancerPancreasDiagnosisLangerhansUnveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity
Bodansky A, Yu D, Rallistan A, Kalaycioglu M, Boonyaratanakornkit J, Green D, Gauthier J, Turtle C, Zorn K, O'Donovan B, Mandel-Brehm C, Asaki J, Kortbawi H, Kung A, Rackaityte E, Wang C, Saxena A, de Dios K, Masi G, Nowak R, O'Connor K, Li H, Diaz V, Saloner R, Casaletto K, Gontrum E, Chan B, Kramer J, Wilson M, Utz P, Hill J, Jackson S, Anderson M, DeRisi J. Unveiling the proteome-wide autoreactome enables enhanced evaluation of emerging CAR-T therapies in autoimmunity. Journal Of Clinical Investigation 2024, 134: e180012. PMID: 38753445, PMCID: PMC11213466, DOI: 10.1172/jci180012.Peer-Reviewed Original ResearchB-cell maturation antigenImmunomodulatory therapyPlasma cell-targeted therapyCAR-T therapyCell-targeted therapyAutoantibody mediated diseasesCAR-TAnti-CD19Maturation antigenAutoantibody profileAutoreactive antibodiesTargeted therapyPlasma cellsAutoimmune diseasesAutoantibody repertoireTherapyMediated diseasesAutoantibodiesTherapeutic interventionsProteome-wideDisease statesDiseaseImmunological fingerprintPhIP-SeqMinimal effectNuclear-penetrating scleroderma autoantibody inhibits topoisomerase 1 cleavage complex formation
May C, Noble P, Herzog E, Meffre E, Hansen J. Nuclear-penetrating scleroderma autoantibody inhibits topoisomerase 1 cleavage complex formation. Biochemical And Biophysical Research Communications 2024, 720: 150123. PMID: 38759301, DOI: 10.1016/j.bbrc.2024.150123.Peer-Reviewed Original ResearchDiffuse cutaneous systemic sclerosisCutaneous systemic sclerosisAnti-topoisomerase 1Systemic lupus erythematosusDiscovery of autoantibodiesMechanisms of autoimmunityInhibit DNA repairScleroderma autoantibodiesScleroderma subtypeSystemic sclerosisLupus erythematosusAutoantibodiesCancer therapyPathophysiologyReagent resourcesCellular dysfunctionAntibodiesCell nucleiDNA repair
2023
Guidelines for best practices in monitoring established coeliac disease in adult patients
Elli L, Leffler D, Cellier C, Lebwohl B, Ciacci C, Schumann M, Lundin K, Chetcuti Zammit S, Sidhu R, Roncoroni L, Bai J, Lee A, Dennis M, Robert M, Rostami K, Khater S, Comino I, Cebolla A, Branchi F, Verdu E, Stefanolo J, Wolf R, Bergman-Golden S, Trott N, Scudeller L, Zingone F, Scaramella L, Sanders D. Guidelines for best practices in monitoring established coeliac disease in adult patients. Nature Reviews Gastroenterology & Hepatology 2023, 21: 198-215. PMID: 38110546, DOI: 10.1038/s41575-023-00872-2.Peer-Reviewed Original ResearchConceptsCoeliac diseaseLevel of evidenceLife-long gluten-free dietGluten-free dietMucosal atrophyAdult patientsCirculating autoantibodiesFollow-upGenetic predispositionImmunological diseasesRecommendations AssessmentMonitoring PatientsClinical guidelinesEvidence levelPatientsConsumption of glutenDiagnosisDiseaseGuidelinesScientific societiesCEDAutoantibodiesGastroenterologistsAtrophyCancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans
Vylegzhanina A, Bespalov I, Novototskaya-Vlasova K, Hall B, Gleiberman A, Yu H, Leontieva O, Leonova K, Kurnasov O, Osterman A, Dy G, Komissarov A, Vasilieva E, Gehlhausen J, Iwasaki A, Ambrosone C, Tsuji T, Matsuzaki J, Odunsi K, Andrianova E, Gudkov A. Cancer Relevance of Circulating Antibodies Against LINE-1 Antigens in Humans. Cancer Research Communications 2023, 3: 2256-2267. PMID: 37870410, PMCID: PMC10631453, DOI: 10.1158/2767-9764.crc-23-0289.Peer-Reviewed Original ResearchConceptsL1 antigenCancer typesDisease stage 1Discovery of autoantibodiesHigh IgG titersTumor-associated antigensDetermination of immunoreactivityTumor immunoreactivityCirculating AntibodiesIgG titersAntibody responseImmune responseLiver cancerReactive IgGHealthy individualsCurable cancer typesImmune systemAntigenNormal tissuesPatientsCancerEarly detectionElevated levelsCarcinogenic processAutoantibodiesHydroxychloroquine in Stage 1 Type 1 Diabetes.
Libman I, Bingley P, Becker D, Buckner J, DiMeglio L, Gitelman S, Greenbaum C, Haller M, Ismail H, Krischer J, Moore W, Moran A, Muir A, Raman V, Steck A, Toledo F, Wentworth J, Wherrett D, White P, You L, Herold K, Steck A, Greenbaum C, Lord S, Monzavi R, Katz L, Goland R, Muir A, Apperson E, DiMeglio L, Cummings E, Weinstock R, Gaglia J, Campbell F, Cabrera S, Nakhle S, English P, Huynh T, Liljenquist D, Moudiotis C, Duke S, Bosi E, Griffin K, Borg H, Lernmark A, Flynn D, Wilson D, Craig M, Moore W, Wherrett D, Tatovich D, Gitelman S, Philipson L, Haller M, Knip M, Tsalikian E, Baidal D, Thomas I, Moran A, Libman I, White P, Raman V, Raleigh Z, Solorzano C, Rodriguez H, Russell W, So M, Colman P, Couper J, Sherr J. Hydroxychloroquine in Stage 1 Type 1 Diabetes. Diabetes Care 2023, 46: 2035-2043. PMID: 37708415, PMCID: PMC10620539, DOI: 10.2337/dc23-1096.Peer-Reviewed Original ResearchConceptsAnnual ophthalmologic examinationsMedian Follow-UpStage 1 diseaseHydroxychloroquine armPreplanned secondary analysisAutoantibodies to GADData Safety Monitoring BoardAnti-insulin autoantibodiesSafety monitoring boardType 1 diabetesInnate immune responseOphthalmologic examinationPositive autoantibodiesAnti-GADHydroxychloroquine treatmentMonth 6Oral glucoseFollow-upDrug treatmentImmune responseHydroxychloroquineAutoantibodiesTransient decreaseMonitoring boardReduced titersWarm autoantibodies mimicking alloantibodies: Three cases of autoantibodies with unusual antigenic specificity
Jacobs J, Binns T, Abels E, Campos J, Elkabbani R, Kress A, Sostin N, Tormey C. Warm autoantibodies mimicking alloantibodies: Three cases of autoantibodies with unusual antigenic specificity. American Journal Of Clinical Pathology 2023, 160: 561-565. PMID: 37598315, DOI: 10.1093/ajcp/aqad095.Peer-Reviewed Original ResearchConceptsWarm autoantibodiesRed blood cellsAntigenic specificityCase of autoantibodiesCase 1Autoimmune hemolytic anemiaDirect antiglobulin testRBC transfusionPregnant womenTransfusion reactionsAntiglobulin testHemolytic anemiaAutoantibodiesRBC antigensAntibody detectionRBC unitsRare reportsBlood cellsCase 2Immunohematologic testingSignificant hemolysisRhD typingCase 3AlloantibodiesAutoantiIndividual 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 conditionsMOGSerumRelapseCytotoxicityNovel Antimurine Thyroid-Stimulating Hormone Receptor Monoclonal Antibodies
Klee A, Torchia J, Freeman G. Novel Antimurine Thyroid-Stimulating Hormone Receptor Monoclonal Antibodies. Monoclonal Antibodies In Immunodiagnosis And Immunotherapy 2023, 42: 109-114. PMID: 37343169, PMCID: PMC10282802, DOI: 10.1089/mab.2022.0037.Peer-Reviewed Original ResearchConceptsThyroid-stimulating hormoneAnti-TSHR autoantibodiesThyroid-stimulating hormone receptorGraves' diseaseHashimoto's thyroiditisThyroid diseaseG protein-coupled receptorsMonoclonal antibodiesAnti-TSHR antibodiesReceptor monoclonal antibodyProduction of thyroxineImmune attackMouse modelAgonist activityAberrant productionThyroid hormonesAutoantibodiesDiseaseHormone receptorsAntibodiesThyroiditisThyroid proteinsThyroidHormoneRange of affinitiesClinicoserological 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 ResearchCGM Metrics Identify Dysglycemic States in Participants From the TrialNet Pathway to Prevention Study.
Wilson D, Pietropaolo S, Acevedo-Calado M, Huang S, Anyaiwe D, Scheinker D, Steck A, Vasudevan M, McKay S, Sherr J, Herold K, Dunne J, Greenbaum C, Lord S, Haller M, Schatz D, Atkinson M, Nelson P, Pietropaolo M. CGM Metrics Identify Dysglycemic States in Participants From the TrialNet Pathway to Prevention Study. Diabetes Care 2023, 46: 526-534. PMID: 36730530, PMCID: PMC10020029, DOI: 10.2337/dc22-1297.Peer-Reviewed Original ResearchConceptsOral glucose tolerance testNormal oral glucose tolerance testType 1 diabetesDiabetes-related autoantibodiesGlucose levelsCGM metricsTrialNet PathwayPrevention StudyAbnormal oral glucose tolerance testGlucose valuesGlucose tolerance testContinuous glucose monitoring parametersStage 2 participantsRelatives of individualsCGMS assessmentDysglycemic statesTolerance testIdentification of individualsDiabetesNegative testAutoantibodiesProgressionBaseline dataIndividualsParticipantsWarm autoimmune hemolytic anemia with anti‐Jka specificity following babesiosis masquerading as a delayed hemolytic transfusion reaction
Jacobs J, Abels E, Binns T, Tormey C, Sostin N. Warm autoimmune hemolytic anemia with anti‐Jka specificity following babesiosis masquerading as a delayed hemolytic transfusion reaction. Transfusion 2023, 63: 872-876. PMID: 36648131, DOI: 10.1111/trf.17252.Peer-Reviewed Case Reports and Technical NotesConceptsWarm autoimmune hemolytic anemiaDirect antiglobulin testAutoimmune hemolytic anemiaHemolytic transfusion reactionsRed blood cellsRBC transfusionTransfusion reactionsHemolytic anemiaKidd antigensPositive direct antiglobulin testDevelopment of autoantibodiesBabesia microti infectionImmunohematology reference laboratoryColumn agglutination technologyAnti-JkUndetectable parasitemiaAutoantibody statusWarm autoantibodiesRBC antibodiesMicroti infectionAntiglobulin testAntigen specificityAutoantibodiesHealthcare providersAntibody detection
2022
Subdoligranulum chews up joints: how a gut pathobiont can instigate arthritis
Kriegel M. Subdoligranulum chews up joints: how a gut pathobiont can instigate arthritis. Trends In Immunology 2022, 44: 4-6. PMID: 36494272, DOI: 10.1016/j.it.2022.11.006.Commentaries, Editorials and LettersConceptsRheumatoid arthritisSystemic autoimmune responseCertain autoimmune diseasesGnotobiotic mouse modelGut pathobiontSynovial inflammationAutoimmune responseAutoimmune diseasesMouse modelMonoclonal autoantibodiesArthritisGut commensalsHuman gut commensalAutoantibodiesOrigin hypothesisInflammationPathobiontsDiseaseSubdoligranulumAutoantibody mimicry of hormone action at the thyrotropin receptor
Faust B, Billesbølle C, Suomivuori C, Singh I, Zhang K, Hoppe N, Pinto A, Diedrich J, Muftuoglu Y, Szkudlinski M, Saghatelian A, Dror R, Cheng Y, Manglik A. Autoantibody mimicry of hormone action at the thyrotropin receptor. Nature 2022, 609: 846-853. PMID: 35940205, PMCID: PMC9678024, DOI: 10.1038/s41586-022-05159-1.Peer-Reviewed Original ResearchConceptsExtracellular domainMembrane bilayerCryo-electron microscopy structureGraves' diseaseGlycoprotein hormone receptorsTSHR extracellular domainG protein-coupled receptorsSteric clashesThyroid hormone synthesisConformational changesThyrotropin receptorHormone synthesisReceptor activationAutoantibodiesHormone receptorsThyroid hormonesThyrotropinTSHRHormone actionThyroidReceptorsAutoimmune hemolytic anemias and paroxysmal nocturnal hemoglobinuria
Tormey C, Siddon A. Autoimmune hemolytic anemias and paroxysmal nocturnal hemoglobinuria. 2022, 346-363. DOI: 10.1002/9781119719809.ch31.ChaptersParoxysmal nocturnal hemoglobinuriaAutoimmune hemolytic anemiaHemolytic anemiaNocturnal hemoglobinuriaMainstay of therapyChoice of therapyDegree of anemiaBone marrow dysfunctionTypes of symptomsBlood transfusionCold autoantibodiesMarrow dysfunctionRBC destructionPNH patientsPrimary disorderSevere hemolysisRare typeAnemiaAutoantibodiesSingle disorderMedical issuesUnique entityPatientsTherapyHemoglobinuriaClinical and Autoantibody Associations in Antinuclear Antibody–Positive Systemic Sclerosis Lacking Prototypic Autoantibodies
Kruzer K, Marangoni R, Heckler I, Elhage A, Varga J, Hinchcliff M, Carns M, Aren K, Wielgosz A, Nuzzo M, Venkataraman I, Korman B. Clinical and Autoantibody Associations in Antinuclear Antibody–Positive Systemic Sclerosis Lacking Prototypic Autoantibodies. JCR Journal Of Clinical Rheumatology 2022, 29: 47-51. PMID: 35767831, PMCID: PMC10241190, DOI: 10.1097/rhu.0000000000001881.Peer-Reviewed Original Research
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