2022
A 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 pathogenesis
2020
Regulator combinations identify systemic sclerosis patients with more severe disease
Wang Y, Franks JM, Yang M, Toledo DM, Wood TA, Hinchcliff M, Whitfield ML. Regulator combinations identify systemic sclerosis patients with more severe disease. JCI Insight 2020, 5: e137567. PMID: 32721949, PMCID: PMC7526449, DOI: 10.1172/jci.insight.137567.Peer-Reviewed Original ResearchConceptsInterstitial lung diseaseSystemic sclerosisActivity scoreSevere diseaseSevere interstitial lung diseaseSubsets of SScVital capacity declineRodnan skin scoreSubgroup of patientsSystemic sclerosis patientsHeterogeneous autoimmune disorderInternal organ dysfunctionGene expression subsetsSkin gene expressionActivation of regulatorsIntrinsic subsetOrgan dysfunctionSclerosis patientsSkin scoreAutoantibody productionClinical outcomesAutoimmune disordersClinical variablesLung diseaseSkin fibrosisHigh-throughput quantitative histology in systemic sclerosis skin disease using computer vision
Correia C, Mawe S, Lofgren S, Marangoni RG, Lee J, Saber R, Aren K, Cheng M, Teaw S, Hoffmann A, Goldberg I, Cowper SE, Khatri P, Hinchcliff M, Mahoney JM. High-throughput quantitative histology in systemic sclerosis skin disease using computer vision. Arthritis Research & Therapy 2020, 22: 48. PMID: 32171325, PMCID: PMC7071594, DOI: 10.1186/s13075-020-2127-0.Peer-Reviewed Original ResearchConceptsSystemic sclerosisFibrosis scoreQuantitative image featuresBiopsy scorePrimary cohortOutcome measuresSecondary cohortDiagnostic scoreSkin severity scoreSSc clinical trialsRodnan skin scoreLogistic regression modelsControl biopsiesRegression modelsSkin scoreSeverity scoreClinical hallmarkClinical trialsForearm biopsiesSSc skinBiopsy sectionsIndependent cohortPatient basisSSc biopsiesCollagen deposition
2019
Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile
Skaug B, Khanna D, Swindell WR, Hinchcliff ME, Frech TM, Steen VD, Hant FN, Gordon JK, Shah AA, Zhu L, Zheng WJ, Browning JL, Barron AMS, Wu M, Visvanathan S, Baum P, Franks JM, Whitfield ML, Shanmugam VK, Domsic RT, Castelino FV, Bernstein EJ, Wareing N, Lyons MA, Ying J, Charles J, Mayes MD, Assassi S. Global skin gene expression analysis of early diffuse cutaneous systemic sclerosis shows a prominent innate and adaptive inflammatory profile. Annals Of The Rheumatic Diseases 2019, 79: annrheumdis-2019-215894. PMID: 31767698, PMCID: PMC7386329, DOI: 10.1136/annrheumdis-2019-215894.Peer-Reviewed Original ResearchConceptsImmune cell signaturesEarly diffuse systemic sclerosisDiffuse systemic sclerosisLonger disease durationSystemic sclerosisDisease durationCell signatureSSc patientsT cellsEarly diffuse cutaneous systemic sclerosisScleroderma Outcome Study cohortDiffuse cutaneous systemic sclerosisShorter disease durationCutaneous systemic sclerosisRodnan skin scoreCD8 T cellsB cell signaturesCD4 T cellsSystemic sclerosis cohortImmune cell markersClinical trial designDiffuse SSc patientsBiopsy RNAProspective registryClinical course
2018
SAT0486 Myeloablation followed by autologous stem cell rescue leads to normalisation of serum il-6 levels in patients with systemic sclerosis
Bellocchi C, Sullivan K, Goldmuntz E, Ying J, Keyes-Elstein L, Varga J, Hinchcliff M, McSweeney P, Furst D, Nash R, Crofford L, Welch B, Pinckney A, Mayes M, Assassi S. SAT0486 Myeloablation followed by autologous stem cell rescue leads to normalisation of serum il-6 levels in patients with systemic sclerosis. Annals Of The Rheumatic Diseases 2018, 77: 1100. DOI: 10.1136/annrheumdis-2018-eular.3731.Peer-Reviewed Original ResearchSerum IL-6 levelsHematopoietic stem cell transplantationIL-6 levelsStem cell transplantationSystemic sclerosisIL-6IL-12IL-1βSCOT trialDisease durationSSc pathogenesisAutologous hematopoietic stem cell transplantationPro-inflammatory Th1 cytokinesAutologous stem cell rescueAutologous stem cell transplantationSerum IFN-γ levelsBaseline clinical featuresMean disease durationStem cell rescueRodnan skin scoreSerum IL-6Diffuse systemic sclerosisMajority of patientsAvailable serum samplesIFN-γ levelsDiffuse cardiac fibrosis quantification in early systemic sclerosis by magnetic resonance imaging and correlation with skin fibrosis
Lee DC, Hinchcliff ME, Sarnari R, Stark MM, Lee J, Koloms K, Hoffmann A, Carns M, Thakrar A, Aren K, Varga J, Aquino A, Carr JC, Benefield BC, Shah SJ. Diffuse cardiac fibrosis quantification in early systemic sclerosis by magnetic resonance imaging and correlation with skin fibrosis. Journal Of Scleroderma And Related Disorders 2018, 3: 159-169. PMID: 29808171, PMCID: PMC5969530, DOI: 10.1177/2397198318762888.Peer-Reviewed Original ResearchEarly systemic sclerosisT1 mapping parametersSystemic sclerosisSSc patientsDiffuse myocardial fibrosisT1 mapping indicesSkin scoreMyocardial fibrosisSkin fibrosisCardiac structure/functionRodnan skin scoreCardiac magnetic resonance T1 mappingT1 mappingMagnetic resonance imagingMagnetic resonance T1 mappingCardiac involvementCardiovascular evaluationConsecutive patientsClinical studiesPatientsResonance imagingFibrosisFibrosis quantificationCine imagingSclerosisMycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin
Hinchcliff M, Toledo DM, Taroni JN, Wood TA, Franks JM, Ball MS, Hoffmann A, Amin SM, Tan AU, Tom K, Nesbeth Y, Lee J, Ma M, Aren K, Carns MA, Pioli PA, Whitfield ML. Mycophenolate Mofetil Treatment of Systemic Sclerosis Reduces Myeloid Cell Numbers and Attenuates the Inflammatory Gene Signature in Skin. Journal Of Investigative Dermatology 2018, 138: 1301-1310. PMID: 29391252, PMCID: PMC6590516, DOI: 10.1016/j.jid.2018.01.006.Peer-Reviewed Original ResearchConceptsMycophenolate mofetil treatmentMyeloid cell numbersMMF therapyMofetil treatmentSystemic sclerosisInflammatory scoreSkin biopsiesCell numberSkin myeloid cellsMyeloid dendritic cellsHalf of patientsRodnan skin scoreImmune cell numbersInflammatory gene signatureExpression of chemokinesProtein levelsCCL2 protein levelsCCL2 mRNA expressionInflammatory signatureDendritic cellsSkin scoreCCL2 mRNAEleven subjectsMonocyte migrationMyeloid cells
2017
Reliability and Validity of the Tender and Swollen Joint Counts and the Modified Rodnan Skin Score in Early Diffuse Cutaneous Systemic Sclerosis: Analysis from the Prospective Registry of Early Systemic Sclerosis Cohort.
Gordon JK, Girish G, Berrocal VJ, Zhang M, Hatzis C, Assassi S, Bernstein EJ, Domsic RT, Hant FN, Hinchcliff M, Schiopu E, Steen VD, Frech TM, Khanna D. Reliability and Validity of the Tender and Swollen Joint Counts and the Modified Rodnan Skin Score in Early Diffuse Cutaneous Systemic Sclerosis: Analysis from the Prospective Registry of Early Systemic Sclerosis Cohort. The Journal Of Rheumatology 2017, 44: 791-794. PMID: 28298560, PMCID: PMC5457319, DOI: 10.3899/jrheum.160654.Peer-Reviewed Original ResearchConceptsDiffuse cutaneous systemic sclerosisSwollen joint countCutaneous systemic sclerosisRodnan skin scoreMusculoskeletal ultrasoundJoint countSkin scoreSystemic sclerosisEarly diffuse cutaneous systemic sclerosisModified Rodnan skin scoreSystemic sclerosis cohortProspective registryTJCExcellent interMRSSSJCSclerosisContent validityScoresCountRheumatologistsPatientsRegistryCohortAbnormalities
2016
Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity
Lofgren S, Hinchcliff M, Carns M, Wood T, Aren K, Arroyo E, Cheung P, Kuo A, Valenzuela A, Haemel A, Wolters PJ, Gordon J, Spiera R, Assassi S, Boin F, Chung L, Fiorentino D, Utz PJ, Whitfield ML, Khatri P. Integrated, multicohort analysis of systemic sclerosis identifies robust transcriptional signature of disease severity. JCI Insight 2016, 1: e89073. PMID: 28018971, PMCID: PMC5161207, DOI: 10.1172/jci.insight.89073.Peer-Reviewed Original ResearchSSc patientsSystemic sclerosisDisease severityMulticohort analysisHealthy controlsHigh case fatality rateLarge longitudinal trialsSkin severity scoreUnmet critical needRare autoimmune diseaseMonths of treatmentRodnan skin scoreConnective tissue diseaseCase fatality rateSkin samplesPotential clinical utilitySkin biopsy samplesRobust molecular signatureSSc cohortSkin scoreTissue diseaseAutoimmune diseasesSeverity scorePatient responseDiscovery cohortThe association between systemic sclerosis disease manifestations and esophageal high‐resolution manometry parameters
Kimmel JN, Carlson DA, Hinchcliff M, Carns MA, Aren KA, Lee J, Pandolfino JE. The association between systemic sclerosis disease manifestations and esophageal high‐resolution manometry parameters. Neurogastroenterology & Motility 2016, 28: 1157-1165. PMID: 26921101, PMCID: PMC4956560, DOI: 10.1111/nmo.12813.Peer-Reviewed Original ResearchConceptsHigh-resolution manometrySSc disease durationClinical characteristicsMotility diagnosisNormal motilityHigh-resolution manometry parametersSevere esophageal dysfunctionWorse lung functionIneffective esophageal motilityPulmonary function testsRetrospective chart reviewRodnan skin scoreSkin disease severitySymptoms of dysphagiaAbsent contractilityEsophageal dysfunctionChart reviewSkin involvementSSc patientsLung functionSkin scoreSystemic manifestationsSystemic sclerosisEsophageal contractilityEsophageal motilityEsophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study
Richardson C, Agrawal R, Lee J, Almagor O, Nelson R, Varga J, Cuttica MJ, Dematte J, Chang RW, Hinchcliff ME. Esophageal dilatation and interstitial lung disease in systemic sclerosis: A cross-sectional study. Seminars In Arthritis And Rheumatism 2016, 46: 109-114. PMID: 27033049, PMCID: PMC5500283, DOI: 10.1016/j.semarthrit.2016.02.004.Peer-Reviewed Original ResearchConceptsRadiographic interstitial lung diseaseSSc interstitial lung diseaseInterstitial lung diseaseSystemic sclerosisCross-sectional studyEsophageal diameterEsophageal dilatationLung diseaseProgression of ILDSSc disease subtypesPulmonary function testsRodnan skin scoreErythrocyte sedimentation rateSecondary outcome variablesBody mass indexGround-glass opacitiesProton pump inhibitorsLow lung volumesSemi-quantitative scoreRegistry patientsDisease durationLow DLCOSkin scoreMedication useSerum autoantibodiesThe relationship between skin symptoms and the scleroderma modification of the health assessment questionnaire, the modified Rodnan skin score, and skin pathology in patients with systemic sclerosis
Ziemek J, Man A, Hinchcliff M, Varga J, Simms RW, Lafyatis R. The relationship between skin symptoms and the scleroderma modification of the health assessment questionnaire, the modified Rodnan skin score, and skin pathology in patients with systemic sclerosis. Rheumatology 2016, 55: 911-917. PMID: 26880832, PMCID: PMC5854039, DOI: 10.1093/rheumatology/kew003.Peer-Reviewed Original ResearchConceptsRodnan skin scoreHealth Assessment QuestionnaireSkin symptomsSkindex-29Skin scoreAssessment QuestionnaireSkin diseasesSkin pathologySSc skin diseaseSymptom assessment questionnairePatient's skin symptomsSSc patientsSystemic sclerosisAtopic dermatitisPathological featuresSymptom assessmentPhysical examMyofibroblast infiltrationPathological changesPathological measuresPatientsSymptom instrumentsSymptomsDiseaseSHAQ
2014
Antinuclear antibody-negative systemic sclerosis
Salazar GA, Assassi S, Wigley F, Hummers L, Varga J, Hinchcliff M, Khanna D, Schiopu E, Phillips K, Furst DE, Steen V, Baron M, Hudson M, Taillefer SS, Pope J, Jones N, Docherty P, Khalidi NA, Robinson D, Simms RW, Silver RM, Frech TM, Fessler BJ, Molitor JA, Fritzler MJ, Segal BM, Al-Kassab F, Perry M, Yang J, Zamanian S, Reveille JD, Arnett FC, Pedroza C, Mayes MD. Antinuclear antibody-negative systemic sclerosis. Seminars In Arthritis And Rheumatism 2014, 44: 680-686. PMID: 25578738, PMCID: PMC4447614, DOI: 10.1016/j.semarthrit.2014.11.006.Peer-Reviewed Original ResearchConceptsANA-negative groupANA-negative patientsPulmonary arterial hypertensionAntinuclear antibodiesSSc patientsDiffuse cutaneous involvementLower gastrointestinal involvementNegative antinuclear antibodyRight heart catheterizationScleroderma Family RegistrySSc-related antibodiesRodnan skin scoreSystemic sclerosis patientsANA-positive patientsRenal crisisVasculopathic manifestationsCause mortalityCutaneous involvementGastrointestinal involvementArterial hypertensionChart reviewClinical characteristicsHeart catheterizationMale patientsSkin score
2012
Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker?
Lakota K, Wei J, Carns M, Hinchcliff M, Lee J, Whitfield ML, Sodin-Semrl S, Varga J. Levels of adiponectin, a marker for PPAR-gamma activity, correlate with skin fibrosis in systemic sclerosis: potential utility as biomarker? Arthritis Research & Therapy 2012, 14: r102. PMID: 22548780, PMCID: PMC3446479, DOI: 10.1186/ar3827.Peer-Reviewed Original ResearchConceptsLevels of adiponectinPPAR-gamma activitySerum adiponectin levelsSystemic sclerosisAdiponectin levelsSkin fibrosisSSc patientsSkin scoreDiffuse cutaneous systemic sclerosisPeroxisome proliferator-activated receptor gammaCutaneous systemic sclerosisRodnan skin scoreProliferator-activated receptor gammaHuman subcutaneous preadipocytesProgression of fibrosisAdiponectin mRNA expressionAdiponectin gene expressionTransforming growth factor betaSignificant inverse correlationLongitudinal study changesGrowth factor betaProgressive fibrosisReal-time quantitative PCRAdiponectin expressionHealthy controls