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
2020
Profibrotic Activation of Human Macrophages in Systemic Sclerosis
Bhandari R, Ball MS, Martyanov V, Popovich D, Schaafsma E, Han S, ElTanbouly M, Orzechowski NM, Carns M, Arroyo E, Aren K, Hinchcliff M, Whitfield ML, Pioli PA. Profibrotic Activation of Human Macrophages in Systemic Sclerosis. Arthritis & Rheumatology 2020, 72: 1160-1169. PMID: 32134204, PMCID: PMC7329566, DOI: 10.1002/art.41243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, CDAntigens, Differentiation, MyelomonocyticCell DifferentiationChemokine CCL2Coculture TechniquesFemaleFibroblastsFibrosisHLA-DR AntigensHumansImmunophenotypingInterleukin-6Lectins, C-TypeLeukocytes, MononuclearMacrophage ActivationMacrophagesMaleMannose ReceptorMannose-Binding LectinsMiddle AgedMonocytesPhosphorylationReceptor, Transforming Growth Factor-beta Type IReceptor, Transforming Growth Factor-beta Type IIReceptors, Cell SurfaceRNA, MessengerScleroderma, SystemicSkinSTAT3 Transcription FactorTranscriptomeTransforming Growth Factor betaConceptsPeripheral blood mononuclear cellsSystemic sclerosisSSc patientsBasal conditionsSex-matched healthy controlsSSc fibroblastsSurface markersHealthy donor monocytesBlood mononuclear cellsMediator of fibrosisInflammatory macrophage activationMonocyte-derived macrophagesActivation profilesGrowth factor βFibrotic activationGene expression signaturesDonor monocytesMononuclear cellsProfibrotic activationSkin fibrosisInterleukin-6Healthy controlsSSc skinIndependent cohortMacrophage activation
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 cohortGenetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients
Wu M, Assassi S, Salazar GA, Pedroza C, Gorlova OY, Chen WV, Charles J, Taing ML, Liao K, Wigley FM, Hummers LK, Shah AA, Hinchcliff M, Khanna D, Schiopu E, Phillips K, Furst DE, Steen V, Baron M, Hudson M, Zhou X, Pope J, Jones N, Docherty P, Khalidi NA, Robinson D, Simms RW, Silver RM, Frech TM, Fessler BJ, Fritzler MJ, Molitor JA, Segal BM, Movahedian M, Martín J, Varga J, Mayes MD. Genetic susceptibility loci of idiopathic interstitial pneumonia do not represent risk for systemic sclerosis: a case control study in Caucasian patients. Arthritis Research & Therapy 2016, 18: 20. PMID: 26792595, PMCID: PMC4719560, DOI: 10.1186/s13075-016-0923-3.Peer-Reviewed Original ResearchConceptsIdiopathic interstitial pneumoniaInterstitial lung diseaseInterstitial pneumoniaValidation cohortSeverity of ILDGenetic susceptibility lociSSc-related interstitial lung diseaseSingle nucleotide polymorphismsCase-control studyGenome-wide association studiesBackgroundSystemic sclerosisSSc-ILDLung involvementSSc patientsSystemic sclerosisVital capacityLung diseaseCaucasian patientsHealthy controlsDiscovery cohortSusceptibility lociPositive subsetControl studyReplication cohortCohort
2012
Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro.
Hinchcliff M, Huang CC, Ishida W, Fang F, Lee J, Jafari N, Wilkes M, Bhattacharyya S, Leof E, Varga J. Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro. Clinical And Experimental Rheumatology 2012, 30: s86-96. PMID: 22691216, PMCID: PMC3860597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBiopsyCase-Control StudiesCells, CulturedFibroblastsFibrosisGene Expression ProfilingGene Expression RegulationHumansImatinib MesylateMiceMice, KnockoutOligonucleotide Array Sequence AnalysisPhosphorylationPiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-ablPyrimidinesScleroderma, SystemicSignal TransductionSkinTime FactorsTranscription, GeneticTransforming Growth Factor beta1ConceptsSystemic sclerosisSSc fibroblastsSkin biopsiesInternal organ fibrosisHeterogeneous multifactorial diseaseControl fibroblastsControl skin biopsiesFibrotic gene expressionSystemic sclerosis fibroblastsC-AblProgressive skinAntifibrotic effectsImatinib mesylateHealthy controlsCardiovascular diseaseGene expressionHealthy subjectsFibrotic responseCholesterol metabolismOrgan fibrosisC-Abl activationMultifactorial diseaseTreatment resultsTissue levelsFibrosisLevels 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
2011
Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
Gorlova O, Martin JE, Rueda B, Koeleman BP, Ying J, Teruel M, Diaz-Gallo LM, Broen JC, Vonk MC, Simeon CP, Alizadeh BZ, Coenen MJ, Voskuyl AE, Schuerwegh AJ, van Riel PL, Vanthuyne M, van 't Slot R, Italiaander A, Ophoff RA, Hunzelmann N, Fonollosa V, Ortego-Centeno N, González-Gay MA, García-Hernández FJ, González-Escribano MF, Airo P, van Laar J, Worthington J, Hesselstrand R, Smith V, de Keyser F, Houssiau F, Chee MM, Madhok R, Shiels PG, Westhovens R, Kreuter A, de Baere E, Witte T, Padyukov L, Nordin A, Scorza R, Lunardi C, Lie BA, Hoffmann-Vold AM, Palm Ø, García de la Peña P, Carreira P, , Varga J, Hinchcliff M, Lee AT, Gourh P, Amos CI, Wigley FM, Hummers LK, Hummers J, Nelson J, Riemekasten G, Herrick A, Beretta L, Fonseca C, Denton C, Gregersen P, Agarwal S, Assassi S, Tan F, Arnett F, Radstake T, Mayes M, Martin J. Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy. PLOS Genetics 2011, 7: e1002178. PMID: 21779181, PMCID: PMC3136437, DOI: 10.1371/journal.pgen.1002178.Peer-Reviewed Original ResearchConceptsSystemic sclerosisSSc patientsHLA regionDiffuse cutaneous involvementHLA-DQB1 lociNon-HLA genesCutaneous involvementHealthy controlsIndependent associationHLA-DQB1Antibody subgroupsIndependent cohortGenome-wide association studiesClinical phenotypeGenetic componentIRF8 geneLcSScSclerosisPatientsSubgroupsCohortSuggestive associationAssociationNovel genetic markersGWAS level