Serum allergens and innate lymphoid cells in eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a recently recognized disorder characterized
by an abnormal accumulation of eosinophils in the esophageal mucosa in patients
with symptoms of dysphagia and esophageal food impaction which typically
requires repeated emergency endoscopies to remove impacted food. Long-term
presence of the disorder leads to fibrotic strictures and diffuse narrowing in
the esophagus that require endoscopic dilatations with a risk of perforation.
A potential allergic pathway in the pathophysiology of this disorder is
suggested by the observation that a large proportion of EoE patients has an
atopic constitution. Estimates of IgE mediated food hypersensitivity in
patients with EoE range from 15 to 43%.
Hypoallergenic foods and medical treatment with corticosteroids are effective,
but the disease almost always recurs upon discontinuation. Furthermore,
treatment with topical or systemic corticosteroids is accompanied by various
side-effects and therefore less suitable for long-term use.

Diagnosis is currently based on symptoms and abnormal histopathology, requiring
endoscopy to take biopsies. No studies have been published that would clearly
permit diagnosis on biomarkers. Furthermore, no reliable biomarker of
inflammation has been identified yet, necessitating endoscopy to confirm
control over the inflammatory process after treatment. Possible future
biomarkers include serum eotaxin-3, plasma basic fibroblast growth factor and
serum IL-15. Results on this subject are shortly expected from current U.S.
studies.

The family of innate lymphoid cells (ILCs) is emerging as a group of critical
players in innate immunity and tissue remodeling. Recently, a new member of the
ILC family, termed ILC2, was identified. This cell type produces very high
levels of the cytokines IL-5 and IL-13, known to be involved in allergy and
EoE. Since ILC2 produce high amounts of IL-5 and IL-13, these cells may
contribute to the pathology of EoE.

Primary: to analyze serum samples of adult EoE patients for IgE reactivity to
recombinant allergens of common foods.

Secondary: to demonstrate the presence of ILC2 in periferal blood of adult
patients with eosinophilic esophagitis

Tertiary: To store serum for future studies aimed at determining biomarkers for
eosinophilic esophagitis before and after 8 weeks of standard PPI treatment.

This observational cohort study has a prospective design. The duration of the
study will be three years.

EoE patients will donate 30 mL of blood off treatment and 10 mL after 8 weeks
of standard PPI treatment
- For future identification of biomarkers for disease and clinical response to
therapy, venous blood samples will be drawn twice in all patients; once off
treatment and once after 8 weeks of standard PPI treatment. In this context, 10
mL of serum will be immediately stored.
- For analysis of food specific IgE, two Sarstedt serum probes of 5 mL will be
collected once and stored.
- For isolation of circulating ILC2, 10 mL of serum is collected once.
Initially, analysis of ILC2 will be performed in 10 patients. When ILC2 cannot
be found in the peripheral circulation of these patients, analysis will not be
performed in the other patients. The number of ILC2 will be determined
immediately in 5 mL of serum. The other 5 mL will be stored for further
analysis on this subject.

Participating in this study results in blood withdrawal either through the
infusion needle which is already in situ for endoscopy, or through vana
puncture. The extent of the burden is considered minimal. Blood withdrawal is
associated with only a slight risk of bleeding/hematoma, infection or
thrombophlebitis.