Role of Mast Cells (an Immune Cell) and Food-Specific IgE Antibodies in Abrupt Food-Induced Response of the Esophagus (FIRE) in Adults with Eosinophilic Esophagitis

Principal Investigator: Joshua Wechsler, MD An allergic/immune condition, the inflammatory process of eosinophilic esophagitis (EoE) leads to chronic swallowing problems and food impaction. These symptoms develop when large numbers of white blood cells called eosinophils build up in the inner lining of the esophagus. EoE is on the rise in the United States, contributing to more than $1.4 billion in health care costs annually. Recently, EoE patients have been found to experience abrupt food-induced responses of the esophagus (FIRE). Symptoms occur immediately after the ingestion of foods that don’t typically trigger eosinophilic inflammation. Preliminary data from Dr. Ikuo Hirano of the Northwestern Medicine Digestive Health Center suggests these patients are sensitized to specific allergy-related antibodies directed at FIRE-associated foods. An antibody linked to food allergies, IgE typically involve mast cells—immune cells present within tissues such as the esophagus that are increased in patients with EoE. Dr. Wechsler’s study will examine esophageal biopsies to determine whether IgE is present on mast cells and whether increased IgE+ mast cells are increased in patients with FIRE when compared to those without FIRE...

Immune Cell Memory Markers Identify Food Triggers in Eosinophilic Esophagitis

Principal Investigator: Joshua Wechsler, MD Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus. Specific foods can trigger esophageal inflammation leading to pain, difficulty swallowing and malnutrition. Elimination diets remain a mainstay for identifying triggers since effective biomarkers or testing are currently nonexistent in this chronic disease. Previous work of Dr. Wechsler’s team revealed an immune response of white blood cells (T-cell receptors) in patients with active EoE who underwent rigorous dietary elimination and reintroduction regimens. Pursuing this promising line of research, Dr. Wechsler intends to examine esophageal biopsies for evidence of the specific immune response of white blood cells to specific foods. The investigators will use deep sequencing of the T-lymphocyte receptor to identify how frequently certain types of T-cells exist between adults with similar and unique food triggers. Findings from this study could open the door to building a digital library of T-cell receptors that identify specific foods and allow for more personalized...

Molecular Changes in Scleroderma Esophageal Disease

Principal Investigator: Marie-Pier Tétreault, PhD Scleroderma is considered an autoimmune disease (the immune system erroneously attacks the body) causing stiffening of the body’s connective tissues of numerous organs leading to stiffening and functional disruptions. More than 95 percent of scleroderma patients develop GI problems, with the esophagus being the most commonly affected organ. Weakening muscle tissue and impairing function, scleroderma esophageal disease can result in complications such as gastroesophageal reflux (GERD), Barrett’s esophagus, and/or adenocarcinoma. Despite efforts to better understand the nature of scleroderma in multiple organs, how scleroderma damages the esophagus remains unclear. Consequently, no treatment exists to change the course of scleroderma esophageal disease. Determining the molecular mechanisms underlying the disease process is critical to developing effective therapies. Using a powerful new technology called single-cell RNA sequencing (scRNA-seq), Dr. Tétreault will examine esophageal biopsies from patients with scleroderma esophageal disease. By pinpointing specific molecular changes in this patient population compared to those of healthy patients, her team hopes to identify novel targets for diagnosis and treatment of this complex...

Which molecular changes are causing the development of eosinophilic esophagitis?

Principal Investigator: Marie-Pier Tetreault, PhD Patients with eosinophilic esophagitis (EoE), a chronic immune/allergic condition affecting children and adults, develop difficulty swallowing food and food obstructions in the esophagus (food tube between the mouth and stomach).  Dr. Tetreault’s team has created a new mouse model that more accurately replicates the disease process of EoE and exhibit all the features observed in patients with the disease. This game changing animal model offers a unique opportunity to better understand the molecular mechanisms driving EoE. By performing “single-cell RNA sequencing”, Dr. Tetreault hopes to determine how changes in specific molecules in epithelial cells control the development of eosinophilic esophagitis. The team will perform these studies in mice that currently have the disease as well as in mice that have yet to show any obvious signs or symptoms. Dr. Tetreault believes that the early-stage disease models will help identify the initiating molecular events that lead to EoE and provide insight into the development of earlier intervention strategies now lacking in the field of...

Evaluating a novel endoscopic ultra sound-guided technique for tissue acquisition for diagnosing pancreatic tumors

The thought of potentially having cancer is stressful enough without undergoing an invasive biopsy to diagnose it and finding out that the procedure needs to be repeated due to inadequate sample collection. This project aims to optimize strategies for acquiring tissue samples to assist gastroenterologists (and pathologists) in diagnosing many diseases, including cancers. Relying on endoscopic ultrasound guidance, the two methods currently utilized are fine needle aspiration, which is the gold standard, and a new method called fine needle biopsy. Drs. Komanduri and Schenck are conducting the largest study to date to compare these different strategies. After collecting data from patients who have undergone one of these procedures over a five-year period, the investigator will perform advanced statistical modeling to determine the strategy that best optimizes patient outcomes (including obtaining accurate diagnoses and minimizing repeat invasive procedures) and costs. Once identified, this strategy will ultimately be implemented throughout the Northwestern Digestive Health Center to enhance patient...