Exploratory Transcriptome Analysis of Human Esophageal Mucosal Biopsies Reveals a Molecular Signature of Type 2 Inflammatory Signaling in Some Patients with Achalasia

Background: It has been hypothesized that achalasia might result from a type 2 inflammatory disorder that draws activated eosinophils and/or mast cells into esophageal muscle. Methods: To seek support for this hypothesis, we probed an existing RNA-sequencing dataset from esophageal biopsies of achalasia patients for molecular signatures of type 2 inflammation. Results: Mucosal biopsies from achalasia patients showed significant enrichment for IL-4 response genes, and 7 of 14 patients exhibited unique gene expression signatures of type 2 inflammation. Conclusion: These findings are consistent with the hypothesis that a subset of achalasia patients exhibits a mucosal type 2 inflammatory transcriptome.