2024
Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease
Yang M, Lee S, Neely J, Hinchcliff M, Wolters P, Sirota M. Gene expression meta-analysis reveals aging and cellular senescence signatures in scleroderma-associated interstitial lung disease. Frontiers In Immunology 2024, 15: 1326922. PMID: 38348044, PMCID: PMC10859856, DOI: 10.3389/fimmu.2024.1326922.Peer-Reviewed Original ResearchConceptsScleroderma-associated interstitial lung diseaseSSc-ILDInterstitial lung diseaseLung tissueGene expression meta-analysisPulmonary fibrosisLung diseaseSenescence signatureDegree of skin involvementIdiopathic pulmonary fibrosisTelomere lengthType II alveolar cellsCellular senescence signaturesCellular senescenceIndependent of ageSkin involvementSSc skinExpression meta-analysisHealthy controlsAssociated with degreeAlveolar cellsLungMeta-analysisAging genesFibrosis
2023
IL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4Clinical Phenotypes of Patients With Systemic Sclerosis With Distinct Molecular Signatures in Skin
Yang M, Goh V, Lee J, Espinoza M, Yuan Y, Carns M, Aren K, Chung L, Khanna D, McMahan ZH, Agrawal R, Nelson L, Shah SJ, Whitfield ML, Hinchcliff M. Clinical Phenotypes of Patients With Systemic Sclerosis With Distinct Molecular Signatures in Skin. Arthritis Care & Research 2023, 75: 1469-1480. PMID: 35997480, PMCID: PMC9947190, DOI: 10.1002/acr.24998.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseInterstitial lung diseaseHigher mRSSSSc patientsSerum autoantibodiesClinical phenotypeHealthy participantsScl-70 antibodyPresent multicenter studySimilar disease durationSystemic sclerosis patientsDistinct clinical phenotypesSkin gene expressionValuable clinical informationDcSSc patientsDisease durationIdentifies patientsSystemic sclerosisSclerosis patientsMulticenter studyLung diseaseSkin fibrosisSimilar prevalenceClinical dataMultivariable modelingImpaired left-ventricular global longitudinal strain by feature-tracking cardiac MRI predicts mortality in systemic sclerosis
Feher A, Miller E, Peters D, Mojibian H, Sinusas A, Hinchcliff M, Baldassarre L. Impaired left-ventricular global longitudinal strain by feature-tracking cardiac MRI predicts mortality in systemic sclerosis. Rheumatology International 2023, 43: 849-858. PMID: 36894756, DOI: 10.1007/s00296-023-05294-6.Peer-Reviewed Original ResearchConceptsLate gadolinium enhancementLV-GLSSystemic sclerosisWorse survivalClinical indicationsImpaired left ventricular global longitudinal strainLeft ventricular global longitudinal strainPresence of LGECMR strainLV cardiac indexWorse LV-GLSLV ejection fractionCox regression analysisGlobal longitudinal strainLV cardiac outputGlobal radialCardiac indexOverall survivalRetrospective cohortEjection fractionPrognostic valueAdverse outcomesCardiac outputGadolinium enhancementRV strainA Novel MIP-1-Expressing Macrophage Subtype in BAL Fluid from Healthy Volunteers.
Reyfman PA, Malsin ES, Khuder B, Joshi N, Gadhvi G, Flozak AS, Carns MA, Aren K, Goldberg IA, Kim S, Alexander M, Sporn PHS, Misharin AV, Budinger GRS, Lam AP, Hinchcliff M, Gottardi CJ, Winter DR. A Novel MIP-1-Expressing Macrophage Subtype in BAL Fluid from Healthy Volunteers. American Journal Of Respiratory Cell And Molecular Biology 2023, 68: 176-185. PMID: 36174229, PMCID: PMC9986555, DOI: 10.1165/rcmb.2021-0123oc.Peer-Reviewed Original ResearchConceptsSingle-cell genomic technologiesCell typesSet of genesSingle-cell approachesSingle-cell RNASingle-cell dataSingle-cell studiesAmbient RNAGenomic technologiesMarker genesGene expressionCellular heterogeneityCellular environmentProtein 1RNAMacrophage heterogeneityGenesValuable resourceDistinct subpopulationsMacrophage subtypesHealthy volunteersLung environmentMacrophage subpopulationsMacrophage inflammatory protein-1Inflammatory protein-1Three Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients
Makinde H, Dunn JLM, Gadhvi G, Carns M, Aren K, Chung AH, Muhammad LN, Song J, Cuda CM, Dominguez S, Pandolfino JE, D'Amico J, Budinger GS, Assassi S, Frech TM, Khanna D, Shaeffer A, Perlman H, Hinchcliff M, Winter DR. Three Distinct Transcriptional Profiles of Monocytes Associate with Disease Activity in Scleroderma Patients. Arthritis & Rheumatology 2023, 75: 595-608. PMID: 36281773, PMCID: PMC10165944, DOI: 10.1002/art.42380.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisNonclassical monocytesClassical monocytesSSc patientsTranscriptional signatureSystemic sclerosisSkin diseasesCharacteristic transcriptional signaturesRNA-seq dataSSc skin diseaseWorse lung functionCutaneous systemic sclerosisEarly systemic sclerosisActivity outcome measuresDistinct transcriptional profilesTranscriptional profilingRNA sequencingTranscriptional profilesProspective registryDisease activityLung functionComplex clinical phenotypeGene expressionPeripheral bloodMinority cell populationHyperspectral imaging in systemic sclerosis-associated Raynaud phenomenon
Teaw S, Gupta A, Williams A, Wilson F, Sumpio B, Sumpio B, Hinchcliff M. Hyperspectral imaging in systemic sclerosis-associated Raynaud phenomenon. Arthritis Research & Therapy 2023, 25: 10. PMID: 36670487, PMCID: PMC9854186, DOI: 10.1186/s13075-023-02990-3.Peer-Reviewed Original ResearchConceptsRaynaud's condition scoreCochin Hand Function ScaleSSc patientsClinic settingPatient-reported outcome instrumentsResultsNinety-two percentSystemic sclerosis patientsMann-Whitney U testHealthy control participantsCHF scoreSSc durationSSc-RPDigital ulcersCutaneous SScProvocation challengeRaynaud's phenomenonSclerosis patientsClinical trialsOutcome instrumentsOxygen saturationBurden assessmentPatientsCold provocationHemoglobin concentrationDisease severityLearnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease
Higuero Sevilla J, Memon A, Hinchcliff M. Learnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease. Arthritis Research & Therapy 2023, 25: 118. PMID: 37422652, PMCID: PMC10329300, DOI: 10.1186/s13075-023-03090-y.Peer-Reviewed Original ResearchConceptsConnective tissue disease-associated interstitial lung diseaseInterstitial lung diseaseTreatment of patientsMycophenolate mofetilSSc-ILDLung diseaseClinical trialsScleroderma Lung Study IIPatient-reported outcome instrumentsIdiopathic inflammatory myositisClinical trial resultsInflammatory myositisIntravenous cyclophosphamideOral cyclophosphamideSubcutaneous tocilizumabGood tolerabilityLung functionSystemic sclerosisTreatment armamentariumRheumatoid arthritisPatient outcomesSimilar efficacyOutcome instrumentsPatientsUS Food
2022
Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis–Associated Interstitial Lung Disease
Yang MM, Balmert LC, Marangoni RG, Carns M, Hinchcliff M, Korman BD, Varga J. Circulating CTRP9 Is Associated With Severity of Systemic Sclerosis–Associated Interstitial Lung Disease. Arthritis Care & Research 2022, 75: 152-157. PMID: 34251759, PMCID: PMC9233895, DOI: 10.1002/acr.24749.Peer-Reviewed Original ResearchConceptsC1q/tumor necrosis factor-related protein 9Interstitial lung diseaseSystemic sclerosisLung diseaseLung functionSystemic Sclerosis-Associated Interstitial Lung DiseaseSSc-associated interstitial lung diseasePulmonary function test dataLatent trajectory analysisVital capacity percentWorse lung functionPrimary outcome measureWorse pulmonary functionCause of morbidityRetrospective longitudinal studyAdipose tissue metabolismCross-sectional analysisAdipokine homeostasisDisease stabilityPulmonary functionSSc patientsSerum levelsPatient RegistryPredictive markerCapacity percentHuman dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis
Bhandari R, Yang H, Kosarek NN, Smith AE, Garlick JA, Hinchcliff M, Whitfield ML, Pioli PA. Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis. Rheumatology 2022, 62: si114-si124. PMID: 35946522, PMCID: PMC9910573, DOI: 10.1093/rheumatology/keac453.Peer-Reviewed Original ResearchConceptsFibroblast-derived exosomesSSc patientsMacrophage activationGender-matched control subjectsSSc fibroblastsDonor-derived macrophagesReciprocal activationUpregulated surface expressionMHC class IICo-cultured macrophagesHealthy control fibroblastsExtracellular matrix depositionCell typesSystemic sclerosisHealthy ageIL-10Production of collagenIL-12p40IL-6Control subjectsSkin biopsiesSSc skinTherapeutic targetingClass IIFlow cytometryDifferences in symptom experience among patients with systemic sclerosis: a cluster analytic approach to identifying subgroups
Murphy SL, Chen YT, Lee YC, Carns M, Aren K, Korman B, Hinchcliff M, Varga J. Differences in symptom experience among patients with systemic sclerosis: a cluster analytic approach to identifying subgroups. Rheumatology 2022, 62: si64-si73. PMID: 35920770, PMCID: PMC9910572, DOI: 10.1093/rheumatology/keac444.Peer-Reviewed Original ResearchConceptsSleep disturbancesSymptom experienceSymptom subgroupsSymptom clustersTreatment approachesSingle US academic medical centerLarge SSc cohortPatient-reported symptomsCo-occurring painUS academic medical centersSymptoms of peopleDistinct symptom clustersAcademic medical centerMain symptom clustersSimilar disease severityDifferent symptom presentationsSSc cohortSSc patientsSystemic sclerosisPain interferencePatient subgroupsModerate symptomsMedical CenterSymptom presentationDisease severityClinical 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 ResearchA genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis
Franks JM, Toledo DM, Martyanov V, Wang Y, Huang S, Wood TA, Spino C, Chung L, Denton C, Derrett-Smith E, Gordon JK, Spiera R, Domsic R, Hinchcliff M, Khanna D, Whitfield ML. A genomic meta-analysis of clinical variables and their association with intrinsic molecular subsets in systemic sclerosis. Rheumatology 2022, 62: 19-28. PMID: 35751592, PMCID: PMC9788818, DOI: 10.1093/rheumatology/keac344.Peer-Reviewed Original ResearchConceptsMolecular subsetsIntrinsic subsetInflammatory subsetBaseline demographicsSSc patientsWhite/Caucasian patientsBaseline clinical demographicsAverage disease durationRodnan skin scoreAfrican American/BlackASSET trialUnique gene expression signatureDisease durationGene expression signaturesClinical demographicsParticipant seraSkin scoreSystemic sclerosisValidation cohortClinical variablesCaucasian patientsSpecific therapyAmerican/BlackSkin biopsiesDisease pathogenesisLung Injury Induces Alveolar Type 2 Cell Hypertrophy and Polyploidy with Implications for Repair and Regeneration.
Weng A, Maciel Herrerias M, Watanabe S, Welch LC, Flozak AS, Grant RA, Aillon RP, Dada LA, Han SH, Hinchcliff M, Misharin AV, Budinger GRS, Gottardi CJ. Lung Injury Induces Alveolar Type 2 Cell Hypertrophy and Polyploidy with Implications for Repair and Regeneration. American Journal Of Respiratory Cell And Molecular Biology 2022, 66: 564-576. PMID: 35202558, PMCID: PMC9116356, DOI: 10.1165/rcmb.2021-0356oc.Peer-Reviewed Original ResearchConceptsLung injuryCell hypertrophyAT2 cellsAlveolar epithelial injuryIntegrated stress responseDistal lung epitheliumBleomycin injuryEpithelial injuryLung epitheliumInjuryBarrier restorationHypertrophic growthSmall molecule ISRIBWound healingFacultative progenitorsHypertrophyStress responseAT2BinucleationCellsReinjuryShort termEpitheliumResponseHigh-throughput identification of autoantibodies that target the human exoproteome
Wang EY, Dai Y, Rosen CE, Schmitt MM, Dong MX, Ferré EMN, Liu F, Yang Y, González-Hernández JA, Meffre E, Hinchcliff M, Koumpouras F, Lionakis MS, Ring AM. High-throughput identification of autoantibodies that target the human exoproteome. Cell Reports Methods 2022, 2: 100172. PMID: 35360706, PMCID: PMC8967185, DOI: 10.1016/j.crmeth.2022.100172.Peer-Reviewed Original ResearchConceptsSystemic lupus erythematosusAutoimmune polyglandular syndrome type 1Specific clinical manifestationsPatient health outcomesSyndrome type 1Numerous autoantibodiesUnidentified autoantibodiesLupus erythematosusClinical manifestationsHuman extracellular proteinsAPS-1Potent biological effectsAutoantibodiesHealth outcomesDisease severityAntigen profilingType 1Patient samplesFunctional effectsPatientsBiological effectsYeast surface display libraryDisplay libraryCell signalingSurface display library
2021
FDG PET vascular imaging in IgG4-RD: Potential and challenges
Pucar D, Hinchcliff M. FDG PET vascular imaging in IgG4-RD: Potential and challenges. Journal Of Nuclear Cardiology 2021, 29: 2934-2937. PMID: 34964084, DOI: 10.1007/s12350-021-02887-1.Peer-Reviewed Original ResearchCellular and Molecular Diversity in Scleroderma
Hinchcliff M, Garcia-Milian R, Di Donato S, Dill K, Bundschuh E, Galdo FD. Cellular and Molecular Diversity in Scleroderma. Seminars In Immunology 2021, 58: 101648. PMID: 35940960, DOI: 10.1016/j.smim.2022.101648.Peer-Reviewed Original ResearchConceptsSystemic sclerosisMedicine approachVariable clinical outcomesPrecision medicine approachPersonalized medicine approachClinical outcomesSame diagnosisDisease heterogeneityDisease riskCare promisesPatient heterogeneityRoutine integrationMolecular heterogeneityMolecular underpinningsSclerosisPatientsSclerodermaHistopathologyMolecular basisArmamentariumFindingsDiagnosisHeterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of “scleroderma esophagus”
Carlson DA, Prescott JE, Germond E, Brenner D, Carns M, Correia CS, Tetreault M, McMahan ZH, Hinchcliff M, Kou W, Kahrilas PJ, Perlman HR, Pandolfino JE. Heterogeneity of primary and secondary peristalsis in systemic sclerosis: A new model of “scleroderma esophagus”. Neurogastroenterology & Motility 2021, 34: e14284. PMID: 34709690, PMCID: PMC9046463, DOI: 10.1111/nmo.14284.Peer-Reviewed Original ResearchConceptsHigh-resolution manometryIneffective esophageal motilitySecondary peristalsisSystemic sclerosisFLIP panometryAbsent contractilityContractile responseDistensibility indexFunctional luminal imaging probe (FLIP) panometryEsophagogastric junction distensibility indexPattern of contractilityEGJ-DIScleroderma esophagusEsophageal dysmotilityReflux severitySSc patientsClinical outcomesEsophageal motilityManometric diagnosisPrimary peristalsisMotor abnormalitiesNormal peristalsisEsophageal functionChicago ClassificationPatientsAssociation Between Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography Imaging and Adverse Events in Patients With Autoimmune Rheumatic Disease
Feher A, Boutagy NE, Oikonomou EK, Liu YH, Miller EJ, Sinusas AJ, Hinchcliff M. Association Between Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography Imaging and Adverse Events in Patients With Autoimmune Rheumatic Disease. Circulation Cardiovascular Imaging 2021, 14: e012208. PMID: 34503339, PMCID: PMC8475774, DOI: 10.1161/circimaging.120.012208.Peer-Reviewed Original ResearchConceptsAutoimmune rheumatic diseasesMyocardial flow reserveLower myocardial flow reserveCox regression analysisAdverse eventsARDS diagnosisIndependent predictorsRheumatic diseasesPerfusion defectsFlow reserveNormal myocardial flow reserveLeft ventricular ejection fractionEnd pointGlobal myocardial flow reserveImpaired Myocardial Flow ReserveComorbidity-matched patientsSevere coronary calcificationCombined end pointCoronary microvascular dysfunctionHeart failure admissionsComposite end pointEvent-free survivalFramingham risk scoreLarge perfusion defectsRetrospective cohort analysisImpaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography/Computed Tomography in Patients With Systemic Sclerosis.
Feher A, Boutagy NE, Oikonomou EK, Thorn S, Liu YH, Miller EJ, Sinusas AJ, Hinchcliff M. Impaired Myocardial Flow Reserve on 82Rubidium Positron Emission Tomography/Computed Tomography in Patients With Systemic Sclerosis. The Journal Of Rheumatology 2021, 48: 1574-1582. PMID: 34266986, PMCID: PMC10275580, DOI: 10.3899/jrheum.210040.Peer-Reviewed Original ResearchConceptsReduced Myocardial Flow ReserveMyocardial flow reserveRaynaud's phenomenonPrimary Raynaud's phenomenonSecondary Raynaud's phenomenonPatient controlsHealthy participantsFlow reservePositron Emission Tomography/Computed TomographyEmission Tomography/Computed TomographyTomography/Computed TomographyPositron emission tomography/Impaired Myocardial Flow ReserveCoronary microvascular dysfunctionLarge prospective studiesMultivariable logistic regressionEmission tomography/PET/CTSSc-RPMicrovascular dysfunctionClinical predictorsIndependent predictorsSystemic sclerosisPrognostic valueProspective study