Discovery of Role of Certain Immune Cells in Increasingly Diagnosed Esophagus Disease (EoE) in Children

Principal Investigator: Joshua Wechsler, MD, MS, Attending Physician, Gastroenterology, Hepatology and Nutrition; CURED (Campaign Urging Research for Eosinophilic Disease) Foundation Research Scholar, Assistant Professor of Pediatrics (Gastroenterology, Hepatology, and Nutrition) and Medicine (Allergy and Immunology), Northwestern University Feinberg School of Medicine Eosinophilic Esophagitis (EoE) is a chronic immune disorder of the esophagus caused by certain foods triggering an allergic response, or by chronic GERD (Gastroesophageal reflux disease/acid reflux). Over time, chronic inflammation from EoE can lead to fibrosis (scarring) and subsequent esophageal stiffness and narrowing of the esophagus. Patients experience difficulty passing food and impaction when food becomes trapped in the esophagus. Identifying early signs and drivers of scarring would help prevent the development of these and other serious complications. Endoscopic Functional Luminal Impedance Probe (EndoFLIP) is used to measure esophageal distensibility (stiffness or stretchiness). Prior research has demonstrated that eosinophils—a type of immune cell—have a weak association with esophageal distensibility. While different types of immune cells play a role in EoE, the association of non-eosinophil immune cells has never been studied. Dr. Wechsler is examining the correlation between esophageal distensibility and non-eosinophil immune cell populations in children with EoE. The team expects this work will guide future studies on EndoFLIP, as well as how immune cells, such as mast cells and T-cells, impact esophageal fibrosis to help develop targeted treatments for EoE that can inhibit disease progression and its destructive effects on pediatric...

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...

Understanding Immune Signature of Foods in Eosinophilic Esophagitis

In Eosinophilic Esophagitis (EoE), a variety of foods trigger inflammation in the esophagus.  Diet elimination remains a mainstay treatment approach, with the number and type of food triggers varying between patients. Some respond well to eliminating a single food while others require the removal of multiple foods. Although no biomarkers or testing currently exist to help pinpoint specific triggers, previous studies have found a key role for white blood cells known as T-cells. This study will assess the novel association between individual food triggers and T-cell clonality. Dr. Wechsler and his team intend to examine esophageal biopsies for evidence of the specificity of immune response of white blood cells to specific foods. The researchers will use deep sequencing of the T-lymphocyte receptor to identify how frequently unique types of T-cells appear. The team hopes this data will help explain how the immune system “learns” to respond to specific foods and, ultimately, provide a potential...