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 activationHigh-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
2015
Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated with Distinct Subsets of Systemic Sclerosis Patients in Three Independent Cohorts
Johnson ME, Mahoney JM, Taroni J, Sargent JL, Marmarelis E, Wu MR, Varga J, Hinchcliff ME, Whitfield ML. Experimentally-Derived Fibroblast Gene Signatures Identify Molecular Pathways Associated with Distinct Subsets of Systemic Sclerosis Patients in Three Independent Cohorts. PLOS ONE 2015, 10: e0114017. PMID: 25607805, PMCID: PMC4301872, DOI: 10.1371/journal.pone.0114017.Peer-Reviewed Original ResearchConceptsNormal-like subsetsGenome-wide expression profilingSet of genesDifferential gene expressionDistinct signaling pathwaysInflammatory subsetSystemic sclerosisGene signatureIndependent cohortGene expression signaturesLipid signalingInnate immune pathwaysActive TGFβ signalingExpression profilingSystemic sclerosis patientsMolecular relationshipsGene expressionNon-lesional skinTGFβ signalingSignaling pathwaysSubsets of diseaseMolecular pathwaysMicroarray datasetsExpression signaturesEarly disease pathology
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