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 cohortTenascin-C drives persistence of organ fibrosis
Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X, Lafyatis R, Lee J, Hinchcliff M, Feghali-Bostwick C, Lakota K, Budinger GR, Raparia K, Tamaki Z, Varga J. Tenascin-C drives persistence of organ fibrosis. Nature Communications 2016, 7: 11703. PMID: 27256716, PMCID: PMC4895803, DOI: 10.1038/ncomms11703.Peer-Reviewed Original ResearchConceptsSystemic sclerosisToll-like receptorsOrgan fibrosisFibrosis resolutionPathogenesis of SScTreatment of SScLevels of tenascinEndogenous danger signalsSSc skin biopsy samplesSkin biopsy samplesMechanism of actionLung fibrosisPathogenic roleTLR activatorsMouse modelBiopsy samplesFibroblast activationDanger signalsMyofibroblast transformationFibrosisSSc fibroblastsCollagen gene expressionSkin fibroblastsAmplification loopTenascin