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 ResearchMeSH KeywordsAgingCellular SenescenceGene ExpressionHumansIdiopathic Pulmonary FibrosisLung Diseases, InterstitialScleroderma, SystemicConceptsScleroderma-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
Clinical 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 ResearchMeSH KeywordsAutoantibodiesFibrosisHumansLung Diseases, InterstitialPhenotypeScleroderma, SystemicSkinConceptsRadiographic 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 strainThree 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 ResearchMeSH KeywordsBiomarkersHumansMacrophagesMonocytesScleroderma, DiffuseScleroderma, LocalizedScleroderma, SystemicSkinConceptsDiffuse 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 ResearchMeSH KeywordsFemaleHumansHyperspectral ImagingMaleRaynaud DiseaseScleroderma, LocalizedScleroderma, SystemicConceptsRaynaud'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 ResearchMeSH KeywordsCross-Sectional StudiesHumansLongitudinal StudiesLungLung Diseases, InterstitialRetrospective StudiesScleroderma, SystemicVital CapacityConceptsC1q/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 ResearchMeSH KeywordsCells, CulturedExosomesFibroblastsFibrosisHumansInflammationMacrophage ActivationScleroderma, SystemicSkinConceptsFibroblast-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 ResearchMeSH KeywordsAnxietyCluster AnalysisDepressionFatigueFemaleHumansMalePainQuality of LifeScleroderma, SystemicSleep Wake DisordersSyndromeConceptsSleep 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 ResearchMeSH KeywordsGenomicsHumansMaleOligonucleotide Array Sequence AnalysisRNAScleroderma, SystemicSkinTranscriptomeConceptsMolecular 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 pathogenesis
2021
Cellular 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 ResearchMeSH KeywordsAdultAgedEsophageal Motility DisordersFemaleHumansManometryMiddle AgedPeristalsisScleroderma, SystemicConceptsHigh-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 ClassificationPatientsEsophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis
Showalter K, Hoffmann A, Richardson C, Aaby D, Lee J, Dematte J, Agrawal R, Savas H, Wu X, Chang RW, Hinchcliff M. Esophageal Dilation and Other Clinical Factors Associated With Pulmonary Function Decline in Patients With Systemic Sclerosis. The Journal Of Rheumatology 2021, 48: 1830-1838. PMID: 34266985, PMCID: PMC8985598, DOI: 10.3899/jrheum.210533.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseInterstitial lung diseasePulmonary function testsSystemic sclerosisEsophageal dilationPulmonary function declineFVC declineClinical factorsEsophageal diameterFunction declineScl-70 positivitySSc-ILD patientsSubanalysis of patientsScl-70Function testsPrognostic implicationsVital capacityLung diseaseStudy criteriaI autoantibodiesRisk factorsPFT declineDiffusion capacityPatientsLinear mixed effects modelsImpaired 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 ResearchMeSH KeywordsFemaleHumansMalePositron Emission Tomography Computed TomographyRubidiumScleroderma, SystemicConceptsReduced 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 studyClinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort
Jaafar S, Lescoat A, Huang S, Gordon J, Hinchcliff M, Shah AA, Assassi S, Domsic R, Bernstein EJ, Steen V, Elliott S, Hant F, Castelino FV, Shanmugam VK, Correia C, Varga J, Nagaraja V, Roofeh D, Frech T, Khanna D. Clinical characteristics, visceral involvement, and mortality in at-risk or early diffuse systemic sclerosis: a longitudinal analysis of an observational prospective multicenter US cohort. Arthritis Research & Therapy 2021, 23: 170. PMID: 34127049, PMCID: PMC8201684, DOI: 10.1186/s13075-021-02548-1.Peer-Reviewed Original ResearchMeSH KeywordsCohort StudiesHumansLung Diseases, InterstitialMycophenolic AcidProspective StudiesScleroderma, DiffuseScleroderma, SystemicUnited StatesConceptsDiffuse cutaneous systemic sclerosisInterstitial lung diseaseImmunosuppressive therapyProgression of skinCardiac involvementSystemic sclerosisUS cohortAnti-RNA polymerase III antibodiesProgressive interstitial lung diseaseEarly diffuse systemic sclerosisMean HAQ-DIMulticenter prospective cohortMulticenter US cohortVital capacity declineMedian disease durationCurrent immunosuppressive therapiesCutaneous systemic sclerosisInternal organ involvementPolymerase III antibodiesDiffuse systemic sclerosisLimited cutaneous SScHigh case fatalityLongitudinal analysisBaseline mRSHAQ-DIPredictive Significance of Serum Interferon‐Inducible Protein Score for Response to Treatment in Systemic Sclerosis–Related Interstitial Lung Disease
Assassi S, Li N, Volkmann ER, Mayes MD, Rünger D, Ying J, Roth MD, Hinchcliff M, Khanna D, Frech T, Clements PJ, Furst DE, Goldin J, Bernstein EJ, Castelino FV, Domsic RT, Gordon JK, Hant FN, Shah AA, Shanmugam VK, Steen VD, Elashoff RM, Tashkin DP. Predictive Significance of Serum Interferon‐Inducible Protein Score for Response to Treatment in Systemic Sclerosis–Related Interstitial Lung Disease. Arthritis & Rheumatology 2021, 73: 1005-1013. PMID: 33350170, PMCID: PMC8169525, DOI: 10.1002/art.41627.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedBeta 2-MicroglobulinChemokine CCL19Chemokine CCL8Chemokine CXCL10Chemokine CXCL9CyclophosphamideFemaleHumansImmunosuppressive AgentsLung Diseases, InterstitialMaleMethotrexateMiddle AgedMycophenolic AcidObservational Studies as TopicPrognosisRandomized Controlled Trials as TopicReceptors, Tumor Necrosis Factor, Type IIScleroderma, SystemicVital CapacityConceptsInterstitial lung diseaseMycophenolate mofetilPredictive significanceCYC armILD courseMMF armSSc-ILDSystemic sclerosisLung diseaseHigh baseline C-reactive protein levelsTumor necrosis factor receptor type IIBaseline C-reactive protein levelsScleroderma Lung Study IIC-reactive protein levelsGood responseVital capacity percentChemotactic protein-2Receptor type IIActive immunosuppressionClinical predictorsCRP levelsObservational cohortProtein scoreActive treatmentTreatment armsA review and roadmap of the skin, lung and gut microbiota in systemic sclerosis
Teaw S, Hinchcliff M, Cheng M. A review and roadmap of the skin, lung and gut microbiota in systemic sclerosis. Rheumatology 2021, 60: 5498-5508. PMID: 33734316, PMCID: PMC8643452, DOI: 10.1093/rheumatology/keab262.Peer-Reviewed Original ResearchLarge‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis
Bellocchi C, Ying J, Goldmuntz EA, Keyes‐Elstein L, Varga J, Hinchcliff ME, Lyons MA, McSweeney P, Furst DE, Nash R, Crofford LJ, Welch B, Goldin JG, Pinckney A, Mayes MD, Sullivan KM, Assassi S. Large‐Scale Characterization of Systemic Sclerosis Serum Protein Profile: Comparison to Peripheral Blood Cell Transcriptome and Correlations With Skin/Lung Fibrosis. Arthritis & Rheumatology 2021, 73: 660-670. PMID: 33131208, PMCID: PMC8005427, DOI: 10.1002/art.41570.Peer-Reviewed Original ResearchMeSH KeywordsAdultChemokinesCytokinesFemaleFibrosisHumansLungMaleMiddle AgedPulmonary FibrosisScleroderma, SystemicSkinSkin DiseasesTranscriptomeConceptsDiffuse cutaneous systemic sclerosisInterstitial lung diseaseSerum protein profilesHealthy control subjectsControl subjectsSex-matched healthy control subjectsRodnan skin thickness scoreSevere interstitial lung diseaseCutaneous systemic sclerosisMean disease durationDiffuse cutaneous SScWhole blood gene expression profilingSkin thickness scoreBlood gene expression profilingPeripheral blood cellsCancer antigen 15Epidermal growth factor receptorSoluble epidermal growth factor receptorSerum proteinsGrowth factor receptorDisease activityDisease durationSystemic sclerosisCutaneous SScImmunosuppressive agentsComputer vision applied to dual-energy computed tomography images for precise calcinosis cutis quantification in patients with systemic sclerosis
Chandrasekaran AC, Fu Z, Kraniski R, Wilson FP, Teaw S, Cheng M, Wang A, Ren S, Omar IM, Hinchcliff ME. Computer vision applied to dual-energy computed tomography images for precise calcinosis cutis quantification in patients with systemic sclerosis. Arthritis Research & Therapy 2021, 23: 6. PMID: 33407814, PMCID: PMC7788847, DOI: 10.1186/s13075-020-02392-9.Peer-Reviewed Original ResearchMeSH KeywordsCalcinosisComputersHumansImage Processing, Computer-AssistedNeural Networks, ComputerScleroderma, SystemicTomographyConceptsSSc patientsCalcinosis cutisCC lesionsSystemic sclerosisBland-Altman plotsConcordance correlation coefficientIndependent radiologistsLin's concordance correlation coefficientConfidence intervalsValid clinical trialsExpert musculoskeletal radiologistsSpearman correlation coefficientClinical trialsMusculoskeletal radiologistsPatientsBurden quantificationLesionsMean differenceGold standardRadiologistsCorrelation coefficientLonger lengthPhalanxSpearman's rhoValidation study