Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures

Jaclyn N. Taroni, Viktor Martyanov, Chiang Ching Huang, J. Matthew Mahoney, Ikuo Hirano, Brandon Shetuni, Guang Yu Yang, Darren Brenner, Barbara Jung, Tammara A. Wood, Swati Bhattacharyya, Orit Almagor, Jungwha Lee, Arlene Sirajuddin, John Varga, Rowland W. Chang, Michael L. Whitfield*, Monique Hinchcliff

*Corresponding author for this work

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Introduction: 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.

Original languageEnglish (US)
Article number194
JournalArthritis Research and Therapy
Volume17
Issue number1
DOIs
StatePublished - Jul 29 2015

Fingerprint

Systemic Scleroderma
Pathology
Biopsy
Gene Expression
Smooth Muscle
Fibrosis
Digestive System Endoscopy
Skin
Muscular Atrophy
Esophagitis
Lymphocyte Count
Transcriptome
Autoantibodies
Esophagus
Smooth Muscle Myocytes
Dilatation
Autopsy

ASJC Scopus subject areas

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Taroni, Jaclyn N. ; Martyanov, Viktor ; Huang, Chiang Ching ; Mahoney, J. Matthew ; Hirano, Ikuo ; Shetuni, Brandon ; Yang, Guang Yu ; Brenner, Darren ; Jung, Barbara ; Wood, Tammara A. ; Bhattacharyya, Swati ; Almagor, Orit ; Lee, Jungwha ; Sirajuddin, Arlene ; Varga, John ; Chang, Rowland W. ; Whitfield, Michael L. ; Hinchcliff, Monique. / Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures. In: Arthritis Research and Therapy. 2015 ; Vol. 17, No. 1.
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abstract = "Introduction: 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.",
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Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures. / Taroni, Jaclyn N.; Martyanov, Viktor; Huang, Chiang Ching; Mahoney, J. Matthew; Hirano, Ikuo; Shetuni, Brandon; Yang, Guang Yu; Brenner, Darren; Jung, Barbara; Wood, Tammara A.; Bhattacharyya, Swati; Almagor, Orit; Lee, Jungwha; Sirajuddin, Arlene; Varga, John; Chang, Rowland W.; Whitfield, Michael L.; Hinchcliff, Monique.

In: Arthritis Research and Therapy, Vol. 17, No. 1, 194, 29.07.2015.

Research output: Contribution to journalArticle

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T1 - Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures

AU - Taroni, Jaclyn N.

AU - Martyanov, Viktor

AU - Huang, Chiang Ching

AU - Mahoney, J. Matthew

AU - Hirano, Ikuo

AU - Shetuni, Brandon

AU - Yang, Guang Yu

AU - Brenner, Darren

AU - Jung, Barbara

AU - Wood, Tammara A.

AU - Bhattacharyya, Swati

AU - Almagor, Orit

AU - Lee, Jungwha

AU - Sirajuddin, Arlene

AU - Varga, John

AU - Chang, Rowland W.

AU - Whitfield, Michael L.

AU - Hinchcliff, Monique

PY - 2015/7/29

Y1 - 2015/7/29

N2 - Introduction: 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.

AB - Introduction: 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.

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