2023
IL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasidiomycotaDisease Models, AnimalEndothelial CellsHumansInterleukin-6MiceScleroderma, LocalizedSkinConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4Three 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 ResearchMeSH KeywordsBiomarkersHumansMacrophagesMonocytesScleroderma, DiffuseScleroderma, LocalizedScleroderma, SystemicSkinConceptsDiffuse 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 populationHyperspectral imaging in systemic sclerosis-associated Raynaud phenomenon
Teaw S, Gupta A, Williams A, Wilson F, Sumpio B, Sumpio B, Hinchcliff M. Hyperspectral imaging in systemic sclerosis-associated Raynaud phenomenon. Arthritis Research & Therapy 2023, 25: 10. PMID: 36670487, PMCID: PMC9854186, DOI: 10.1186/s13075-023-02990-3.Peer-Reviewed Original ResearchMeSH KeywordsFemaleHumansHyperspectral ImagingMaleRaynaud DiseaseScleroderma, LocalizedScleroderma, SystemicConceptsRaynaud's condition scoreCochin Hand Function ScaleSSc patientsClinic settingPatient-reported outcome instrumentsResultsNinety-two percentSystemic sclerosis patientsMann-Whitney U testHealthy control participantsCHF scoreSSc durationSSc-RPDigital ulcersCutaneous SScProvocation challengeRaynaud's phenomenonSclerosis patientsClinical trialsOutcome instrumentsOxygen saturationBurden assessmentPatientsCold provocationHemoglobin concentrationDisease severityLearnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease
Higuero Sevilla J, Memon A, Hinchcliff M. Learnings from clinical trials in patients with connective tissue disease-associated interstitial lung disease. Arthritis Research & Therapy 2023, 25: 118. PMID: 37422652, PMCID: PMC10329300, DOI: 10.1186/s13075-023-03090-y.Peer-Reviewed Original ResearchConceptsConnective tissue disease-associated interstitial lung diseaseInterstitial lung diseaseTreatment of patientsMycophenolate mofetilSSc-ILDLung diseaseClinical trialsScleroderma Lung Study IIPatient-reported outcome instrumentsIdiopathic inflammatory myositisClinical trial resultsInflammatory myositisIntravenous cyclophosphamideOral cyclophosphamideSubcutaneous tocilizumabGood tolerabilityLung functionSystemic sclerosisTreatment armamentariumRheumatoid arthritisPatient outcomesSimilar efficacyOutcome instrumentsPatientsUS Food
2020
High-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
2016
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
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
FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling
Bhattacharyya S, Tamaki Z, Wang W, Hinchcliff M, Hoover P, Getsios S, White ES, Varga J. FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling. Science Translational Medicine 2014, 6: 232ra50. PMID: 24739758, PMCID: PMC4414050, DOI: 10.1126/scitranslmed.3008264.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Endogenous TLR4 ligandsCutaneous fibrosisTLR4 ligandToll-like receptor signalingProgressive autoimmune diseaseLesional skin biopsiesFibronectin extra domain ATreatment of fibrosisTissue repair responseHallmark of sclerodermaPersistent fibroblast activationExtra domain ATLR4 blockadeAutoimmune diseasesChronic conditionsChronic fibrosisReceptor 4Skin biopsiesFibrotic responseOrganotypic skin equivalentsMultiple organsPotent stimulusSclerodermaFibroblast activation