Comparison of mast cells and IgE in adult EoE patients with FIRE symptoms

Project: Research project

Project Details

Description

The objective of the proposed research project is to identify the relationship of IgE+ mast cells to FIRE Symptoms in Adults with Eosinophilic Esophagitis

Eosinophilic Esophagitis is a chronic food-allergic disease characterized by intermittent swallowing difficulty. The disease occurs in 1 in 1000 adults, and costs nearly a billion dollars in annual health costs. Recently, a population of adult patients has been identified with rapid intense esophageal symptom term FIRE for food-induced symptoms of the esophagus. Notably, these symptoms are causes by foods that do not typically trigger esophageal eosinophilia. Interestingly, a group from the Europe found esophageal injection of specific foods led to a rapid swelling response. Preliminary data from Northwestern suggests this may be an IgE-mediated phenomenon as EoE patients with FIRE symptoms have evidence of IgE sensitization to specific foods or pollens. Activation via IgE would likely occur on mast cells which have been found to have IgE on their surface in high density in patients with active EoE compared to inactive EoE or non-EoE controls. While treatment with IgE-blocking biologics does not alter eosinophil trafficking to the esophagus, there may be an effect on mast cell activation relevant to a subset of patients. Notably, we found that mast cell inflammation has deleterious effects on mucosal healing. Thus, questions remain including whether mast cells and food-specific IgE is increased in adults with EoE with FIRE symptoms compared to EoE patients without FIRE symptoms.

The aims of the study are: 1) Compare mast cell density between EoE patients with and without FIRE symptoms. 2) Compare food-specific IgE density between EoE patients with and without FIRE symptoms.

For this study, Dr. Hirano will provide de-identified archived formalin-fixed paraffin biopsies from the proximal and distal esophagus on slides (unstained) to the laboratory of Dr. Wechsler. The cohort will be adults with active EoE distinguished with regards to FIRE symptoms by survey. Active EoE is defined by peak eosinophil count of greater than 15 eos/hpf will be present in adjacent standard of care biopsies. The slides will be stained for mast cell marker: tryptase and food-specific IgE (based on patient report of FIRE food). The slides will be imaged and quantified in the laboratory of Dr. Wechsler. Dr. Wechsler will be the primary investigator and supervise the laboratory work.
StatusActive
Effective start/end date6/1/2012/31/21

Funding

  • Northwestern Memorial Hospital (Agmt 7/2/2020)
  • Digestive Health Foundation (Agmt 7/2/2020)

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