TCR clonotype in adults with EoE undergoing food reintroduction

Project: Research project

Project Details

Description

The objective of the proposed research project is to identify biomarkers of dietary triggers associated with Eosinophilic Esophagitis (EoE) in adults.

Eosinophilic Esophagitis is a chronic food-allergic disease that left untreated leads to scarring of the esophagus and resulting food impaction which requires emergent endoscopy. The disease occurs in 1 in 1000 adults, and costs nearly a billion dollars in annual health costs. While a core set of foods exists that are commonly triggers of inflammation in EoE, the number of food triggers is variable among patients. Unlike IgE-mediated food allergies, which are associated with immediate hives and/or anaphylaxis, EoE does not involve the production of food-specific antibodies (IgE). Currently there is no testing to identify food triggers in EoE, and in order to identify specific triggers, patients typically eliminate up to 4-8 foods including dairy, soy, wheat, eggs, nuts, and seafood. After resolution of eosinophilia, patients reintroduce foods one by one with endoscopy required to identify food triggers that elicit inflammation. Thus, patients often eliminate unnecessary foods and undergo unnecessary endoscopies. Testing to rule in/out specific food triggers is needed.

While EoE doesn’t involve food-specific IgE, there appears to be a key role for T-lymphocytes in coordinating the eosinophils to come to the esophagus. T-lymphocytes express a receptor called the T-cell receptor (TCR), whose function is the selective recognition of foreign substances. We hypothesize that a restricted set of TCRs exist that predict specific food triggers. Using previous funding from DHF, we performed pilot studies to assess the TCR in a small number of EoE patients who had undergone diet elimination with identification of specific food triggers along with non-EoE controls. We found patients with active EoE had a more restricted set of TCRs compared to control patients and EoE patients with inactive EoE. In addition, we found that TCRs present at the time of diagnosis recur with food reintroduction of EoE trigger foods, and that several common TCRs occur in patients that share the same food trigger.

The aims of the study are: 1) Validate differences in TCR clonality between EoE patients with active EoE compared to inactive EoE and non-EoE controls and 2) Validate shared TCRs among patients with specific food triggers.

For this study, Dr. Gonsalves will provide de-identified archived biopsies to the laboratory of Dr. Wechsler to isolate total RNA. The cohort will be adults with EoE treated with diet elimination with identified specific food triggers. Active EoE, defined by peak eosinophil count of greater than 15 eos/hpf will be present in adjacent standard of care biopsies. RNA will be isolated and sent to iRepertoire (Huntsville, AB) for TCR sequencing. Dr. Wechsler will be the primary investigator and supervise the laboratory work (RNA isolation) and bioinformatic analysis.
StatusActive
Effective start/end date6/1/2012/31/21

Funding

  • Northwestern Memorial Hospital (#21)
  • Digestive Health Foundation (#21)

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