Immunopathogenesis of Food Allergy and Eosinophilic Gastrointestinal Disorders
Immunopathogenesis of Food Allergy and Eosinophilic Gastrointestinal Disorders
Background:

 - Food allergies are characterized by abnormal immune system responses to certain foods, such
 as peanuts, strawberries, and shellfish. Some individuals with these allergies have immediate
 allergic reactions on contact with the food in question and need immediate treatment to
 prevent severe complications. In contrast, eosinophil-associated gastrointestinal disorders
 are related disorders in which white blood cells in the intestinal tract react to certain
 foods, causing abdominal pain, nausea, and other digestion problems. Researchers are
 interested in studying these conditions to better understand how the immune system responds
 to food allergies.

 Objectives:

 -  To examine how the immune system responds to food allergens.

 -  To examine how certain white blood cells contribute to disease in individuals with food
 allergies and other inflammatory diseases.

 Eligibility:

 -  Individuals between 18 and 65 years of age who have a history of (a) severe allergic
 reaction to peanuts (and have peanut-specific antibodies), (b) allergy or inflammatory
 disease, or (c) eosinophil-associated gastrointestinal disorder (with at least two
 documented food allergies).

 -  Healthy volunteers between 18 and 65 years of age who have no known allergies or asthma.

 Design:

 -  All participants will have a screening visit and a procedure visit. The procedure visit
 will take place within 30 to 60 days of the screening visit, and will take 3 to 4 hours
 depending on the procedure(s) done.

 -  Participants will be screened with a physical examination and medical history, and will
 provide blood samples for testing. Participants with peanut or other allergies will have
 additional tests to determine their levels of sensitivity to certain foods. Participants
 with eosinophil-associated gastrointestinal disorder will provide stool samples for
 testing.

 -  At the procedure visit, participants with peanut allergies and participants with other
 allergies will provide blood samples and have leukapherisis to collect white blood cells
 for examination.

 -  At the procedure visit, healthy volunteers and participants with eosinophil-associated
 gastrointestinal disorder will provide blood samples and have leukapherisis to collect
 white blood cells for examination. In addition, some but not all of these participants
 will have a procedure called esophagogastroduodenoscopy (EGD), which will examine the
 esophagus, stomach, and small intestine. Participants who are scheduled to have EGD will
 be asked to fast for 6 hours before the procedure.
Food allergy refers to a number of disorders characterized by clinical diseases associated
 with abnormal immune responses to food antigens. Classical IgE mediated anaphylactic food
 allergy is characterized by immediate hypersensitivity, and has a prevalence of approximately
 6% and 3% in children and adults, respectively. In contrast, eosinophil associated
 gastrointestinal disorders (EGIDs), including eosinophilic esophagitis (EoE) and eosinophilic
 gastroenteritis (EG), are food allergy associated disorders characterized by eosinophilic
 inflammation of the gut, typically without anaphylaxis. Progress in the treatment and
 management of these food allergies requires further understanding of the immunological
 pathogenesis of these disorders. A subset of peripheral blood food allergen specific
 interleukin (IL) -5 producing T cells that are present in EGID but not peanut allergic
 subjects has recently been characterized. The primary objective of this study is to determine
 if similar IL-5 producing T cells are present in the gut of EGID subjects. To this end, both
 EGID and healthy non-allergic subjects will be enrolled and gastrointestinal biopsies will be
 obtained for intracellular cytokine staining, RT-PCR and ELISA.

 Additionally, this protocol will supply blood and leukapheresis samples for exploratory
 studies on immunologic mechanisms underlying anaphylactic food allergy and EGIDs. A total of
 up to 400 subjects recruited from outside physician referrals and support groups, as well as
 from those in existing National Institutes of Health (NIH) protocols will be enrolled in this
 Clinical Center study.
-  INCLUSION CRITERIA:

 Subjects must meet all of the inclusion criteria:

 All Subjects must:

 1. Be willing to have samples collected and stored for future research.

 2. Have a documented clinical history compatible with EGID, peanut allergy, or other
 allergic and inflammatory diseases or be healthy without known allergic conditions.

 In addition to the above inclusion criteria for all subjects, the subjects in the following
 groups must meet additional group-specific inclusion criteria.

 Subjects with EGID must:

 1. Be greater than or equal to 18 years of age

 2. Maintain a primary non-NIH physician for routine care

 3. Have one of the types of EGID below:

 -  Eosinophilic gastroenteritis: Have a clinical history of eosinophilic
 gastroenteritis -including gastrointestinal symptoms-, and histological evidence
 of stomach or duodenal eosinophilia with no other known etiology for the
 eosinophilia despite careful clinical evaluation.

 OR

 -Eosinophilic esophagitis: Have a diagnosis of eosinophilic esophagitis, including evidence
 of esophageal dysfunction with a peak count of greater than or equal to 25 eosinophils per
 high powered field, for which the biopsy was obtained while under proton pump inhibitor
 treatment.

 OR

 -Probable eosinophilic esophagitis: Have a likely diagnosis of eosinophilic esophagitis,
 based on evidence of esophageal dysfunction and a peak count of greater than or equal to 15
 eosinophils per high powered field, but for which the biopsy was not obtained under proton
 pump inhibitors (per section 6.3). To confirm

 a diagnosis of EoE, these subjects may be treated with proton pump inhibitor therapy at
 recommended doses for gastroesophageal reflux disease for at least 84 weeks prior to EGD
 and biopsy. The decision to recommend diagnostic biopsy will be according to concensus
 guidelines [7] and current standards of care: based on the severity of symptoms, history of
 food impactions, and evidence of remodeling (strictures).

 Subjects with Peanut Allergy:

 1. Be greater than or equal to 18 years of age and less than or equal to 65 years of age.

 2. Have a history of immediate hypersensitivity to peanuts with involvement of at least
 one extracutaneous site, including wheezing, laryngeal edema, angioedema, vomiting,
 diarrhea, hypotension and circulatory collapse.

 3. Have peanut specific IgE of greater than or equal to 5 kIU/L.

 Subjects with Other Allergic and Inflammatory Diseases:

 1. Be greater than or equal to 18 years of age and less than or equal to 65 years of age.

 2. These subjects must be diagnosed with an allergic or an inflammatory disease,
 including anaphylaxis, asthma, or hay fever. Diagnosis will be based on established
 criteria for each clinical entity.

 Healthy, Non-Atopic Subjects:

 1. Be greater than or equal to 18 years of age and less than or equal to 65 years of age.

 2. Have no history of allergies, asthma or food allergy

 3. Have a negative ImmunoCAP fx5 in vitro food allergy screen for allergen specific IgE
 to egg white, milk, cod, wheat, peanut, and soy

 4. Have a negative Phadiatop allergy screen

 EXCLUSION CRITERIA:

 Subjects with any of the following criteria will be excluded:

 1. Any other condition that, in the investigator s opinion, places the subject at undue
 risk by participating in the study

 Subjects with Peanut Allergy with any of the following will be excluded:

 1. Chronic upper GI symptoms that are consistent with EGID (dysphagia, nausea, vomiting,
 abdominal pain/cramps, early satiety)

 PROCEDURAL INCLUSIONS:

 Subjects with EoE and EG undergoing research EGD or lymphapheresis must:

 1. Be greater than or equal to 18 years of age and less than or equal to 65 years of age.

 Subjects with EG undergoing EGD or lymphapheresis must have:

 1. Histological evidence of stomach or duodenal eosinophilia with a peak count greater
 than or equal to 40 eosinophils per high powered field

 2. Greater than two positive allergen skin tests or antigen specific IgE tests out of the
 following panel (peanut, wheat, soy, shrimp, egg white, milk, walnut, cod, corn)

 Subjects with either EG or EoE undergoing lymphapheresis must have:

 1. An absolute eosinophil count of >750 eos/microL at least once in the last 2 years

 Subjects with EoE undergoing EGD must have:

 1. Diagnosed EoE per section 5.1 with a previous biopsy showing greater than or equal to
 25 eosinophils per high powered field, OR

 2. Probable eosinophilic esophagitis per section 5.1 with a previous biopsy showing
 greater than or equal to 25 eosinophils per high powered field

 PROCEDURAL EXCLUSIONS:

 Subjects with any of following will not undergo EGD:

 1. Uncontrolled asthma or Grade 3 or higher by the American Society of Anesthesiologist s
 (ASA) Physical Status Classification System.

 2. History of adverse reaction to conscious sedation required for EGD.

 Subjects with any of following will not undergo EGD or lymphapheresis:

 1. Hemoglobin <12 g/dL

 2. Viral screens positive for HIV or hepatitis B or C

 3. Pregnant or breast-feeding women

 Control Subjects (Healthy, Non-Atopic) Undergoing EGD with any of the following will be
 excluded:

 1. History of reflux or use of acid suppression medication within the last 6 months.

 2. Chronic gastrointestinal disease or immunological disease.

 3. Clinically indicated EGD in the past 12 months.

 4. Use of systemic corticosteroids in the past 6 months.

 EGID subjects who are pregnant or breast-feeding may be followed without research
 phlebotomy.