2024
POS0824 ARTIFICIAL INTELLIGENCE (DEEP NEURAL NETWORK ANALYSIS) AS A SKIN OUTCOME: RESULTS OF AN OPEN-LABEL BELUMOSUDIL TRIAL IN PATIENTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS
Gunes B, Duran Camacho L, Cowper S, Panse G, Page N, Bundschuh E, Williams A, Carns M, Aren K, Pradhan N, Bernstein E, Fantus S, Volkmann E, Bukiri H, Correia C, Wilson F, Mawe S, Mahoney J, Wang R, Hinchcliff M. POS0824 ARTIFICIAL INTELLIGENCE (DEEP NEURAL NETWORK ANALYSIS) AS A SKIN OUTCOME: RESULTS OF AN OPEN-LABEL BELUMOSUDIL TRIAL IN PATIENTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS. 2024, 1046.2-1047. DOI: 10.1136/annrheumdis-2024-eular.2892.Peer-Reviewed Original Research
2023
POS1258 RESULTS FROM A NOMINAL GROUP TECHNIQUE EXERCISE FOR THE CREATION OF A COMBINED RESPONSE INDEX FOR LIMITED CUTANEOUS SYSTEMIC SCLEROSIS: THE CRISTAL PROJECT
Lescoat A, Chen Y, Murphy S, Carroll L, Vann N, Didio P, Iya S, Phanhdone T, Farrington S, Allanore Y, Cella D, Chung L, Clements P, Del Galdo F, Denton C, Distler O, Hinchcliff M, Hughes M, Hummers L, Pauling J, Pope J, Steen V, Varga J, Buch M, Khanna D. POS1258 RESULTS FROM A NOMINAL GROUP TECHNIQUE EXERCISE FOR THE CREATION OF A COMBINED RESPONSE INDEX FOR LIMITED CUTANEOUS SYSTEMIC SCLEROSIS: THE CRISTAL PROJECT. 2023, 971.2-972. DOI: 10.1136/annrheumdis-2023-eular.4633.Peer-Reviewed Original ResearchThree 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 population
2022
Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis
Odell I, Steach H, Gauld S, Reinke-Breen L, Karman J, Carr T, Wetter J, Phillips L, Hinchcliff M, Flavell R. Epiregulin is a dendritic cell–derived EGFR ligand that maintains skin and lung fibrosis. Science Immunology 2022, 7: eabq6691. PMID: 36490328, PMCID: PMC9840167, DOI: 10.1126/sciimmunol.abq6691.Peer-Reviewed Original ResearchConceptsLung fibrosisDendritic cellsImmune cellsDiffuse cutaneous systemic sclerosisPersistence of fibrosisCutaneous systemic sclerosisExtent of fibrosisType I interferonSystemic sclerosisAutoimmune diseasesAntifibrotic targetsTherapeutic administrationMouse modelI interferonLung samplesLung explantsFibrosisFibrotic tissueImmune signalsEpiregulin expressionPatient's skinExtracellular matrix productionGenetic deficiencyEpiregulinEGFR ligands
2021
Clinical 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 ResearchConceptsDiffuse 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-DILarge‐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 ResearchConceptsDiffuse 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 agents
2020
Performance Characteristics of Pulmonary Function Tests for the Detection of Interstitial Lung Disease in Adults With Early Diffuse Cutaneous Systemic Sclerosis
Bernstein EJ, Jaafar S, Assassi S, Domsic RT, Frech TM, Gordon JK, Broderick RJ, Hant FN, Hinchcliff ME, Shah AA, Shanmugam VK, Steen VD, Khanna D. Performance Characteristics of Pulmonary Function Tests for the Detection of Interstitial Lung Disease in Adults With Early Diffuse Cutaneous Systemic Sclerosis. Arthritis & Rheumatology 2020, 72: 1892-1896. PMID: 32583956, PMCID: PMC7722107, DOI: 10.1002/art.41415.Peer-Reviewed Original ResearchConceptsDetection of ILDPulmonary function testsInterstitial lung diseaseDiffuse cutaneous SScEarly diffuse cutaneous systemic sclerosisDiffuse cutaneous systemic sclerosisNegative predictive valueCutaneous systemic sclerosisSystemic sclerosisFunction testsLung diseaseDevelopment of ILDDiagnosis of ILDEarly diffuse cutaneous SScRadiographic interstitial lung diseaseInadequate screening toolsEarly systemic sclerosisRetrospective cohort studyCause of deathProspective registrySSc cohortCohort studyVital capacityHRCT imagingHigh risk
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 courseTowards a new classification of systemic sclerosis
Hinchcliff M, Mahoney JM. Towards a new classification of systemic sclerosis. Nature Reviews Rheumatology 2019, 15: 456-457. PMID: 31217541, DOI: 10.1038/s41584-019-0257-z.Peer-Reviewed Original Research
2017
Brief Report: Association of Elevated Adipsin Levels With Pulmonary Arterial Hypertension in Systemic Sclerosis
Korman BD, Marangoni RG, Hinchcliff M, Shah SJ, Carns M, Hoffmann A, Ramsey‐Goldman R, Varga J. Brief Report: Association of Elevated Adipsin Levels With Pulmonary Arterial Hypertension in Systemic Sclerosis. Arthritis & Rheumatology 2017, 69: 2062-2068. PMID: 28651038, PMCID: PMC5748338, DOI: 10.1002/art.40193.Peer-Reviewed Original ResearchMeSH KeywordsAdiponectinAdultAgedAutoantibodiesComplement Factor DCytokinesFemaleGene Expression ProfilingHumansHypertension, PulmonaryLeptinMaleMiddle AgedNatriuretic Peptide, BrainNicotinamide PhosphoribosyltransferaseOdds RatioPolymorphism, Single NucleotideResistinScleroderma, DiffuseScleroderma, LimitedConceptsSSc-related pulmonary arterial hypertensionPulmonary arterial hypertensionSystemic sclerosisAdipokine levelsComplement pathway activationAdipsin levelsArterial hypertensionLimited cutaneous systemic sclerosisB-type natriuretic peptidePathway activationSerum adipokine levelsCutaneous systemic sclerosisLevels of adiponectinGene single nucleotide polymorphismsAdipose tissue biologyTissue-derived markersAdipokine balanceAutoantibody statusPulmonary functionSSc patientsAdipocyte dysfunctionClinical featuresPathogenic linkClinical manifestationsNatriuretic peptideReliability 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
Molecular Stratification by Gene Expression as a Paradigm for Precision Medicine in Systemic Sclerosis
Hinchcliff M, Whitfield M. Molecular Stratification by Gene Expression as a Paradigm for Precision Medicine in Systemic Sclerosis. 2016, 657-670. DOI: 10.1007/978-3-319-31407-5_49.Peer-Reviewed Original ResearchSystemic sclerosisPatient subsetsProgressive interstitial lung diseaseDiffuse cutaneous systemic sclerosisAppropriate patient subsetsScleroderma renal crisisCutaneous systemic sclerosisInvestigator-initiated trialPulmonary arterial hypertensionSubset of patientsDifferent patient subsetsInterstitial lung diseaseDifferent pathophysiological processesMolecular pathwaysPrecision medicineGene expression subsetsT lymphocyte activationUninvolved skin samplesInflammatory subsetRenal crisisSSc complicationsArterial hypertensionMycophenolate mofetilClinical improvementOrgan involvement
2015
Serum Amyloid A Is a Marker for Pulmonary Involvement in Systemic Sclerosis
Lakota K, Carns M, Podlusky S, Mrak-Poljsak K, Hinchcliff M, Lee J, Tomsic M, Sodin-Semrl S, Varga J. Serum Amyloid A Is a Marker for Pulmonary Involvement in Systemic Sclerosis. PLOS ONE 2015, 10: e0110820. PMID: 25629975, PMCID: PMC4321755, DOI: 10.1371/journal.pone.0110820.Peer-Reviewed Original ResearchConceptsSerum amyloid ASystemic sclerosisPulmonary involvementSSc patientsAmyloid AAcute phase protein serum amyloid AEarly diffuse cutaneous systemic sclerosisEffect of SAAInflammatory marker serum amyloid ALevels of SAAElevated serum amyloid AFrequent interstitial lung diseaseDiffuse cutaneous systemic sclerosisLung fibroblastsRecombinant serum amyloid APatient-reported outcome measuresDiffuse cutaneous involvementCutaneous systemic sclerosisEarly-stage diseaseMarkers of inflammationInterstitial lung diseaseNormal lung fibroblastsDose-dependent stimulationHuman pulmonary fibroblastsCutaneous involvement
2013
Treatment of early diffuse systemic sclerosis skin disease.
Frech TM, Shanmugam VK, Shah AA, Assassi S, Gordon JK, Hant FN, Hinchcliff ME, Steen V, Khanna D, Kayser C, Domsic RT. Treatment of early diffuse systemic sclerosis skin disease. Clinical And Experimental Rheumatology 2013, 31: 166-71. PMID: 23910619, PMCID: PMC3889109.Peer-Reviewed Original ResearchConceptsSSc skin diseaseSystemic sclerosisSkin diseasesEarly diffuse cutaneous systemic sclerosisDiffuse cutaneous systemic sclerosisEarly diffuse SScEarly systemic sclerosisCutaneous systemic sclerosisDiffuse systemic sclerosisIncident cohort studyIntravenous immunoglobulinProspective registryCohort studyInter-institutional variabilityClinical courseHigh morbidityDiffuse SScEffective treatmentNovel biomarkersDisease pathogenesisSclerosisDiseaseTreatmentRigorous studiesMycophenolate
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