2022
An Acute Exacerbation of Idiopathic Pulmonary Fibrosis After BNT162b2 mRNA COVID-19 Vaccination A Case Report
Ghincea A, Ryu C, Herzog EL. An Acute Exacerbation of Idiopathic Pulmonary Fibrosis After BNT162b2 mRNA COVID-19 Vaccination A Case Report. CHEST Journal 2022, 161: e71-e73. PMID: 35131075, PMCID: PMC8814523, DOI: 10.1016/j.chest.2021.07.2160.Peer-Reviewed Case Reports and Technical NotesConceptsIdiopathic pulmonary fibrosisAE-IPFAcute exacerbationPulmonary fibrosisLung diseaseCase reportFatal interstitial lung diseaseMRNA COVID-19 vaccinationChronic lung diseaseInterstitial lung diseaseVaccine-preventable diseasesNovel case reportA Case ReportCOVID-19 vaccinationScar tissue formationRespiratory decompensationAdverse eventsPulmonary embolismVulnerable patientsDrug toxicityPotential associationShort courseDiseaseExacerbationFibrosis
2021
Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones
Glauzy S, Olson B, May CK, Parisi D, Massad C, Hansen JE, Ryu C, Herzog EL, Meffre E. Defective Early B Cell Tolerance Checkpoints in Patients With Systemic Sclerosis Allow the Production of Self Antigen–Specific Clones. Arthritis & Rheumatology 2021, 74: 307-317. PMID: 34279059, PMCID: PMC8766600, DOI: 10.1002/art.41927.Peer-Reviewed Original ResearchConceptsB cell tolerance checkpointsEarly B cell tolerance checkpointsPeripheral B cell tolerance checkpointsNaive B cellsMature naive B cellsSystemic sclerosisTransitional B cellsTolerance checkpointsB cellsHealthy donorsAutoreactive mature naive B cellsAutoreactive naive B cellsAntigen-specific B cellsCentral B cell toleranceB cell toleranceB cell productionAntigen-specific clonesReactivity of antibodiesSingle B cellsSSc patientsSerum autoantibodiesAutoimmune diseasesImmune complexesPatientsCell tolerance
2020
Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease
Ryu C, Walia A, Ortiz V, Perry C, Woo S, Reeves BC, Sun H, Winkler J, Kanyo JE, Wang W, Vukmirovic M, Ristic N, Stratton EA, Meena SR, Minasyan M, Kurbanov D, Liu X, Lam TT, Farina G, Gomez JL, Gulati M, Herzog EL. Bioactive Plasma Mitochondrial DNA Is Associated With Disease Progression in Scleroderma‐Associated Interstitial Lung Disease. Arthritis & Rheumatology 2020, 72: 1905-1915. PMID: 32602227, PMCID: PMC8081728, DOI: 10.1002/art.41418.Peer-Reviewed Original ResearchConceptsCGAS/STING activationExtracellular vesiclesMitochondrial DNAPattern recognition receptorsCyclic GMP-AMP synthase/stimulatorHuman lung fibroblastsSSc-ILD cohortsInterstitial lung diseaseMT-ATP6 geneΑ-SMA expressionI interferonSSc-ILDScleroderma-Associated Interstitial Lung DiseaseSynthetic CpG DNATLR-9Clinical outcomesLung diseaseSTING activationInterleukin-6Enzyme-linked immunosorbent assay-based methodProteomic profilesMulticellular originSystemic sclerosis-associated interstitial lung diseaseImmune pattern recognition receptorsExtracellular mtDNAReduced Sialylation and Bioactivity of the Antifibrotic Protein Serum Amyloid P in the Sera of Patients with Idiopathic Pulmonary Fibrosis
Chen W, Karhadkar TR, Ryu C, Herzog EL, Gomer RH. Reduced Sialylation and Bioactivity of the Antifibrotic Protein Serum Amyloid P in the Sera of Patients with Idiopathic Pulmonary Fibrosis. ImmunoHorizons 2020, 4: 352-362. PMID: 32576593, PMCID: PMC8500545, DOI: 10.4049/immunohorizons.2000043.Peer-Reviewed Original ResearchConceptsSerum amyloid PIPF patientsPulmonary fibrosisFibrocyte differentiationIL-10 accumulationAmyloid PEffects of SAPIdiopathic pulmonary fibrosis (IPF) pathogenesisPulmonary fibrosis pathogenesisIdiopathic pulmonary fibrosisBronchoalveolar lavage fluidSera of patientsHigh extracellular levelsPotential therapeutic targetDifferentiation of monocytesSialic acidIPF pathogenesisIL-10Scar-like tissueLavage fluidHealthy controlsFatal disorderFibrosis pathogenesisHuman PBMCsTherapeutic target
2019
GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis
Zhang Y, Jiang M, Nouraie M, Roth MG, Tabib T, Winters S, Chen X, Sembrat J, Chu Y, Cardenes N, Tuder RM, Herzog EL, Ryu C, Rojas M, Lafyatis R, Gibson KF, McDyer JF, Kass DJ, Alder JK. GDF15 is an epithelial-derived biomarker of idiopathic pulmonary fibrosis. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2019, 317: l510-l521. PMID: 31432710, PMCID: PMC6842909, DOI: 10.1152/ajplung.00062.2019.Peer-Reviewed Original ResearchMeSH KeywordsAgedAlveolar Epithelial CellsAnimalsBleomycinBronchoalveolar Lavage FluidCase-Control StudiesDisease Models, AnimalFemaleGene Expression ProfilingGrowth Differentiation Factor 15HumansIdiopathic Pulmonary FibrosisLungMaleMiceMiddle AgedRespiratory Function TestsSeverity of Illness IndexSurvival AnalysisTelomereTranscriptomeConceptsIdiopathic pulmonary fibrosisBleomycin challengePulmonary fibrosisEpithelial cellsDisease pathologyConcentrations of GDF15Type II alveolar epithelial cellsInterstitial lung diseaseDifferentiation factor 15Multiple independent cohortsAlveolar epithelial cellsLung epithelial cellsIPF patientsPulmonary functionBronchoalveolar lavagePoor outcomeLung diseasePeripheral bloodEpithelial dysfunctionTelomere dysfunctionLung tissueFactor 15Epithelial stressIndependent cohortUseful biomarkerPlasma mitochondrial DNA is associated with extrapulmonary sarcoidosis
Ryu C, Brandsdorfer C, Adams T, Hu B, Kelleher DW, Yaggi M, Manning EP, Walia A, Reeves B, Pan H, Winkler J, Minasyan M, Dela Cruz CS, Kaminski N, Gulati M, Herzog EL. Plasma mitochondrial DNA is associated with extrapulmonary sarcoidosis. European Respiratory Journal 2019, 54: 1801762. PMID: 31273041, PMCID: PMC8088542, DOI: 10.1183/13993003.01762-2018.Peer-Reviewed Original ResearchConceptsExtrapulmonary diseaseMitochondrial DNAExtracellular mtDNABAL fluidAlpha-1 antitrypsin deficiencyPlasma mitochondrial DNAPlasma of patientsAfrican AmericansExtrapulmonary sarcoidosisSarcoidosis cohortSarcoidosis subjectsScadding stageAfrican American descentClinical featuresClinical findingsGranulomatous diseaseHealthy controlsAntitrypsin deficiencyGenomic researchHigher oddsSarcoidosisAggressive phenotypeMechanistic basisDiseaseTherapeutic insightsLMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis
Xie Y, Ostriker AC, Jin Y, Hu H, Sizer AJ, Peng G, Morris AH, Ryu C, Herzog EL, Kyriakides T, Zhao H, Dardik A, Yu J, Hwa J, Martin KA. LMO7 Is a Negative Feedback Regulator of Transforming Growth Factor β Signaling and Fibrosis. Circulation 2019, 139: 679-693. PMID: 30586711, PMCID: PMC6371979, DOI: 10.1161/circulationaha.118.034615.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell ProliferationCells, CulturedDisease Models, AnimalExtracellular MatrixFeedback, PhysiologicalFibrosisHyperplasiaIntegrin alphaVbeta3LIM Domain ProteinsMaleMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleNeointimaSignal TransductionTranscription Factor AP-1Transcription FactorsTransforming Growth Factor beta1Vascular RemodelingVascular System InjuriesConceptsSmooth muscle cellsActivator protein-1 (AP-1) transcription factorExtracellular matrixProtein-1 transcription factorTransforming Growth Factor β SignalingGrowth factor β signalingMouse smooth muscle cellsTGF-β1 target genesHuman smooth muscle cellsActivator protein-1Muscle-specific deletionNegative feedback regulatorTGF-β pathwayECM protein expressionSmad3 phosphorylationNegative feedback regulationTranscription factorsArteriovenous fistulaECM depositionDomain interactsTGF-β proteinTarget genesLMO7TGF-β treatmentGrowth factor β
2018
S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension
Tzouvelekis A, Herazo‐Maya J, Ryu C, Chu J, Zhang Y, Gibson KF, Adonteng‐Boateng P, Li Q, Pan H, Cherry B, Ahmad F, Ford HJ, Herzog EL, Kaminski N, Fares WH. S100A12 as a marker of worse cardiac output and mortality in pulmonary hypertension. Respirology 2018, 23: 771-779. PMID: 29611244, PMCID: PMC6047907, DOI: 10.1111/resp.13302.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsPH patientsPH cohortCardiac outputWorld Health Organization group 1Idiopathic pulmonary fibrosis patientsPulmonary hypertension patientsPulmonary fibrosis patientsBlood mononuclear cellsProtein serum concentrationsHigher S100A12Pulmonary hypertensionS100A12 levelsOverall mortalityHypertension patientsPrognostic valueValidation cohortMononuclear cellsPeripheral bloodSerum concentrationsInflammatory diseasesGroup 1PatientsFibrosis patientsS100A12
2017
Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis
Ryu C, Sun H, Gulati M, Herazo-Maya J, Chen Y, Osafo-Addo A, Brandsdorfer C, Winkler J, Blaul C, Faunce J, Pan H, Woolard T, Tzouvelekis A, Antin-Ozerkis DE, Puchalski JT, Slade M, Gonzalez AL, Bogenhagen DF, Kirillov V, Feghali-Bostwick C, Gibson K, Lindell K, Herzog RI, Dela Cruz CS, Mehal W, Kaminski N, Herzog EL, Trujillo G. Extracellular Mitochondrial DNA Is Generated by Fibroblasts and Predicts Death in Idiopathic Pulmonary Fibrosis. American Journal Of Respiratory And Critical Care Medicine 2017, 196: 1571-1581. PMID: 28783377, PMCID: PMC5754440, DOI: 10.1164/rccm.201612-2480oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisNormal human lung fibroblastsExtracellular mitochondrial DNABronchoalveolar lavageIPF fibroblastsPulmonary fibrosisInnate immune ligandsEvent-free survivalSmooth muscle actin expressionMtDNA concentrationsSmooth muscle actin-expressing myofibroblastsGrowth factor-β1Muscle actin expressionHuman lung fibroblastsTGF-β1 stimulationExtracellular mtDNAIPF cohortClinical outcomesControl subjectsDisease progressionGlycolytic reprogrammingSoluble mediatorsTGF-β1Factor-β1Immune ligands
2016
Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis
Tzouvelekis A, Herazo‐Maya J, Slade M, Chu J, Deiuliis G, Ryu C, Li Q, Sakamoto K, Ibarra G, Pan H, Gulati M, Antin‐Ozerkis D, Herzog EL, Kaminski N. Validation of the prognostic value of MMP‐7 in idiopathic pulmonary fibrosis. Respirology 2016, 22: 486-493. PMID: 27761978, PMCID: PMC5352520, DOI: 10.1111/resp.12920.Peer-Reviewed Original ResearchConceptsTransplant-free survivalIdiopathic pulmonary fibrosisMMP-7 concentrationsMatrix metalloproteinase-7IPF patientsCause mortalityPulmonary fibrosisHealthy controlsMultivariate Cox proportional hazards modelCox proportional hazards modelPulmonary function parametersVariable clinical courseBaseline pulmonary function parametersProportional hazards modelIPF biomarkersProgressive diseaseClinical coursePoor prognosisPrognostic valueVital capacityIndependent biomarkerLung capacityPrognostic thresholdPlasma concentrationsMortality risk