Mast Cell Activation in the Systemic Sclerosis Esophagus

Area of Science:

• Gastroenterology
• Immunology
• Rheumatology

Background:

• Systemic sclerosis (SSc) shares esophageal gene expression patterns with eosinophilic esophagitis (EoE), where mast cell-targeted therapies are effective.
• Similar esophageal symptoms in SSc and EoE suggest potential benefit from eosinophil/mast cell-directed therapies in SSc patients.

Purpose of the Study:

• To determine the association between esophageal mast cell quantities, gene expression, and clinical parameters in SSc.
• To identify SSc patients who may benefit from eosinophil/mast cell-directed therapy.

Main Methods:

• Esophageal biopsies from SSc patients and healthy controls were stained for tryptase (mast cell marker).
• Mast cell density was quantified, and associations with clinical parameters like 24h esophageal pH testing were assessed.
• Microarray data facilitated gene set enrichment analysis and intrinsic subset (IS) assignment.

Main Results:

• Esophageal mast cell numbers correlated significantly with acid exposure time in SSc patients.
• Inflammatory, fibroproliferative, and normal-like intrinsic subsets were identified in esophageal biopsies.
• Upregulated gene expression for mast cell-related pathways was observed in the inflammatory IS of SSc patients.

Conclusions:

• Esophageal mast cell numbers in SSc are heterogeneous and may correlate with acid exposure.
• Patients with inflammatory IS profiles show increased tryptase staining.
• Mast cell-targeted therapy could benefit SSc patients in the inflammatory IS, warranting further investigation.