A Distinct Esophageal mRNA Pattern Stamp Identifies a Subpopulation of EoE Patients With Food Impactions

Abstract

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated inflammatory disorder of esophagus characterized by eosinophil-rich infiltrates. A significant portion of EoE patients suffer from esophageal food impactions. The underlying mechanism of food impactions is not well understood. Food impactions can happen in the absence of an anatomical problem in the esophagus. Previous literature shows evidence for abnormal esophageal motility in EoE patients. This implies that impaired motility of the esophagus is likely the cause of food impactions in EoE patients. Motility in the gastrointestinal tract is under the control of the nervous system. Nitric oxide (NO) is the main inhibitory neurotransmitter that causes relaxation of the smooth muscle in the gastrointestinal tract. NO is synthesized by nitric oxide synthases (NOS). Inducible NOS (iNOS) is an isoform of NOS that is induced in immune cells upon stimulation by proinflammatory cytokines. We hypothesized that low levels of NO due to low expression of iNOS might cause the impaired motility in EoE and result in food impactions. Using a digital mRNA profiling method, we identify a distinct subpopulation of EoE that is characterized by low transcript levels of iNOS and suffers from food impactions. In addition, we show that the esophageal mRNA pattern stamp of this low-iNOS patient subpopulation shows lower expression levels of Th2-type inflammatory markers IL-4, IL-5, eotaxin-1, carboxypeptidase A3, Fc receptors for IgE and OX40L; along with lower expression levels of other inflammatory markers such as IFN-γ, CD14, IL-2, IL-12β, IFN-β1, IL-10, Fc receptors for IgG, CCL2 and CCR3. The ability to prospectively define the subpopulation of EoE patients that is prone to food impactions has important direct implications for clinical practice. Identification of these patients can help clinicians to inform them about the likely course of their EoE phenotype, which can improve their quality of lives. Furthermore, therapeutic strategies for food impactions targeting NO can be developed for future use in this subpopulation.