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dc.contributor.authorTaroni, JN
dc.contributor.authorMartyanov, V.
dc.contributor.authorHuang, C-C
dc.contributor.authorMahoney, JM
dc.contributor.authorHirano, I
dc.contributor.authorShetuni, B.
dc.contributor.authorYang, G-Y
dc.contributor.authorBrenner, D.
dc.contributor.authorJung, B.
dc.date.accessioned2016-02-17T20:09:19Z
dc.date.available2016-02-17T20:09:19Z
dc.date.issued2015
dc.identifier.bibliographicCitationTaroni, Jaclyn N., et al. "Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures." Arthritis research & therapy 17.1 (2015): 1-14. DOI: 10.1186/s13075-015-0695-1.en_US
dc.identifier.issn1478-6354
dc.identifier.urihttp://hdl.handle.net/10027/20273
dc.descriptionThis is the copy of an article published in Arthritis Research and Therapy © 2015 BioMed Central Publications. © 2015 Taroni et al.en_US
dc.description.abstractINTRODUCTION: Esophageal involvement in patients with systemic sclerosis (SSc) is common, but tissue-specific pathological mechanisms are poorly understood. There are no animal scleroderma esophagus models and esophageal smooth muscle cells dedifferentiate in culture prohibiting in vitro studies. Esophageal fibrosis is thought to disrupt smooth muscle function and lead to esophageal dilatation, but autopsy studies demonstrate esophageal smooth muscle atrophy and the absence of fibrosis in the majority of SSc cases. Herein, we perform a detailed characterization of SSc esophageal histopathology and molecular signatures at the level of gene expression. METHODS: Esophageal biopsies were prospectively obtained during esophagogastroduodenoscopy in 16 consecutive SSc patients and 7 subjects without SSc. Upper and lower esophageal biopsies were evaluated for histopathology and gene expression. RESULTS: Individual patient's upper and lower esophageal biopsies showed nearly identical patterns of gene expression. Similar to skin, inflammatory and proliferative gene expression signatures were identified suggesting that molecular subsets are a universal feature of SSc end-target organ pathology. The inflammatory signature was present in biopsies without high numbers of infiltrating lymphocytes. Molecular classification of esophageal biopsies was independent of SSc skin subtype, serum autoantibodies and esophagitis. CONCLUSIONS: Proliferative and inflammatory molecular gene expression subsets in tissues from patients with SSc may be a conserved, reproducible component of SSc pathogenesis. The inflammatory signature is observed in biopsies that lack large inflammatory infiltrates suggesting that immune activation is a major driver of SSc esophageal pathogenesis.en_US
dc.description.sponsorshipThis work was supported in part by a NIH-Eunice Kennedy Shriver NICHD K12 HD055884, a NIH-NIAMS K23 AR059763 and a research award from the Scleroderma Foundation (MH), by the Scleroderma Research Foundation (MH, MLW), by NIH-NIAMS P60 AR064464 (CCH, RWC, JL), NIH P50AR060780 (MLW, JMM, JNT), NIH-NIGMS T32GM008704 (JNT), NIH-NIAMS AR42309 (SB, JV), and NIH-NCI R25 CA134286-01 (JMM), NIH-NCI RO1 CA141057 (BJ) and NIH-NIAMS P30AR061271 (TAW, VM, MLW).en_US
dc.publisherBioMed Centralen_US
dc.titleMolecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signaturesen_US
dc.typeArticleen_US


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