Mast cell activation in the systemic sclerosis esophagus

Kevin Tom, Bhaven K. Mehta, Aileen Hoffmann, Kathleen Aren, Mary Carns, Jungwha Lee, Viktor Martyanov, Dillon Popovich, Noelle Kosarek, Tammara A. Wood, Darren Brenner, Dustin A. Carlson, Lorena Ostilla, Emma Willcocks, Paul Bryce, Joshua B. Wechsler, Michael L. Whitfield, Monique Hinchcliff*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


Introduction: Previously, we discovered similar esophageal gene expression patterns in patients with systemic sclerosis and eosinophilic esophagitis where eosinophil/mast cell–targeted therapies are beneficial. Because systemic sclerosis and eosinophilic esophagitis patients experience similar esophageal symptoms, we hypothesized that eosinophil/mast cell–directed therapy may potentially benefit systemic sclerosis patients. Herein, we determine the association between esophageal mast cell quantities, gene expression, and clinical parameters in order to identify systemic sclerosis patients who may benefit from eosinophil/mast cell–directed therapy. Methods: Esophageal biopsies from systemic sclerosis patients and healthy participants were stained for tryptase, a mast cell marker, and associations with relevant clinical parameters including 24-h esophageal pH testing were assessed. Intra-epithelial mast cell density was quantified by semi-automated microscopy. Microarray data were utilized for functional and gene set enrichment analyses and to identify intrinsic subset assignment, a systemic sclerosis molecular classification system that includes inflammatory, proliferative, limited, and normal-like subsets. Results: Esophageal biopsies from 40 systemic sclerosis patients (39 receiving proton pump inhibition) and eleven healthy participants were studied. Mast cell numbers in both the upper esophagus (rs = 0.638, p = 0.004) and the entire (upper + lower) esophagus (rs = 0.562, p = 0.019) significantly correlated with acid exposure time percentage. The inflammatory, fibroproliferative, and normal-like intrinsic subset originally defined in skin biopsies were identified in esophageal biopsies. Although esophageal mast cell numbers in systemic sclerosis patients and healthy participants were similar, gene expression for mast cell–related pathways showed significant upregulation in the inflammatory intrinsic subset of systemic sclerosis patients compared to patients classified as proliferative or normal-like. Discussion: Esophageal mast cell numbers are heterogeneous in systemic sclerosis patients and may correlate with acid exposure. Patients with inflammatory intrinsic subset profiles in the esophagus demonstrate more tryptase staining. Mast cell–targeted therapy may be a useful therapeutic approach in systemic sclerosis patients belonging to the inflammatory intrinsic subset, but additional studies are warranted.

Original languageEnglish (US)
JournalJournal of Scleroderma and Related Disorders
StateAccepted/In press - 2020


  • Systemic sclerosis
  • eosinophilic esophagitis
  • fibrosis
  • mast cell inflammatory signature
  • mast cells
  • systemic sclerosis esophagus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology


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