Natural History and Genetics of Food Allergy and Related Conditions

There are approximately 15 million Americans, including 6 million children, who have a
potentially life-threatening food allergy. The prevalence of this disease has increased over
the last three decades, in both the United States and other developed countries. There are no
cures or effective prevention or treatment strategies for food allergy. Moreover, little is
known about the factors that account for the rising prevalence and severity of these diseases
in recent years. Both genetic and environmental factors likely contribute to the development
of food allergy, but the complex interaction between these variables has frustrated efforts
to elucidate pathogenesis and develop mechanism-targeted therapies. Children with food
allergy are 2 to 4 times more likely to be diagnosed with asthma or other allergic conditions
than children without food allergy, and food allergy may also be an important trigger for
atopic dermatitis and eosinophilic esophagitis. The Laboratory of Allergic Diseases within
the National Institute of Allergy and Infectious Diseases has a longstanding interest in the
genetics and pathogenesis of allergic inflammatory disorders, and with the National
Institutes of Health Clinical Center, it provides the ideal environment for the proposed
translational studies. In this study, we will: (1) investigate the key genetic, cellular,
immunologic, and biochemical pathways that lead to the development of food allergy, and (2)
identify biomarkers that predict the clinical course and natural history of patients with
food allergy.

Subjects eligible for enrollment in this study include children and adults with food allergy
and patients with a known/suspected genetic or congenital disorder potentially associated
with these phenotypes. Unaffected relatives (children and adults) of an enrolled subject and
healthy volunteers (children and adults) will also be eligible for enrollment as controls.
Most participants will be followed for 2 years, although participants with an identified
genetic or congenital disorder and a subset of participants with food allergy may be followed
until this study ends (up to 12 years).

Data obtained from analysis of blood, skin, saliva, stool, gastrointestinal biopsies, and
other specimens will be used to explore the immunologic, biochemical, microbial, and genetic
basis of food allergy. Results of research studies will be correlated with the scope and
severity of their clinical phenotype, their response to treatment, and the natural history of
their allergic disease(s).

- GENERAL INCLUSION CRITERIA:

All participants must meet the following criteria:

1. Be 2 to 99 years-old at the time on enrollment

2. Willing to allow storage of blood, buccal swabs, saliva, nasal swabs, stool samples,
and other clinically appropriate tissue specimens for future use in medical research

3. Required to have a primary care or other physician who will manage all health
conditions related or unrelated to the study objectives

ADDITIONAL INCLUSION CRITERIA FOR AFFECTED PARTICIPANTS

In addition to the general criteria listed above, affected participants must meet 1 of the
following criteria:

1. Have a clinical history of an immediate hypersensitivity reaction to food(s) and be
sensitized to food allergen(s) (as evidenced by positive SPT or allergen-specific IgE
testing)

2. Be sensitized (as evidenced by positive SPT or allergen-specific IgE testing) to food
allergen(s) but have no overt clinical history of IgE-mediated symptoms when they eat
that food(s)

3. Have a suspected genetic or congenital disorder potentially associated with food
allergy or related condition, as determined by the principal investigator (PI) or
associate investigators (AIs)

Additionally, participants who meet criteria 1 or 3 must have a primary physician outside
of the NIH who must submit a letter or clinical summary that documents the participant s
relevant health history.

ADDITIONAL INCLUSION CRITERIA FOR HEALTHY VOLUNTEERS

In addition to the general criteria listed above , healthy volunteers must meet the
following criteria:

1. Be unrelated to an affected participant

2. Be unaffected by food allergy (as determined by clinical history and/or allergy
testing) or be unaffected by the genetic condition under study

ADDITIONAL PROCEDURE- SPECIFIC INCLUSION CRITERIA:

The following additional inclusion criteria apply for participants undergoing
leukapheresis:

1. Age greater than or equal to 12 years for affected participants; age greater than or
equal to 18 years for unaffected relatives and healthy volunteers

2. Stable hematologic paramaters (definition: white blood cell count > 2,500/ L,
hemoglobin > 10 g/dL, and platelet count > 75,000/microliter)

GENERAL EXCLUSION CRITERIA:

Participants will be excluded for any of the following:

- Presence of conditions that, in the judgment of the investigator or the referring
physician, may put the participant at undue risk or make them unsuitable for
participation in the study.

- Inability to participate for the duration of the study.

- The PI deems that participation in the study would not be expected to advance the
study goals.

ADDITIONAL PROCEDURE- SPECIFIC EXCLUSION CRITERIA

Additional exclusion criteria apply for participants who are undergoing endoscopsy with
biopsies strictly for research purposes. Participants will be excluded from participating
in this procedure if they meet any of the following criteria:

1. uncontrolled asthma or Grade 3 or higher by the American Society of Anesthesiologist
s.Physical Status Classification System
(http://www.asahq.org/resources/clinicalinformation/.asa-physical-status-classificatio
n-system)

2. history of adverse reaction to conscious sedation or general anesthesia required for
endoscopy

3. hemoglobin < 12 g/dL

4. platelet count < 100,000 microL

5. PT INR >1.3 or PTT prolonged by > 3 seconds

6. pregnant or breastfeeding

7. viral screens positive for HIV or hepatitis B or C

8. severe unstable myocardial ischemia or cardiomyopathy

9. severe hypoxemia due to chronic pulmonary disease

10. recent abdominal surgery

11. anticoagulant therapy that cannot be interrupted

Additionally, unaffected relatives and healthy volunteers will be excluded from endoscopy
if they meet any of the following criteria:

1. history of reflux or use of acid-suppression medication (including over-the-counter
medication) within the last 6 months

2. chronic GI or immunologic disease

3. clinically indicated EGD or colonoscopy within the past 12 months

4. use of systemic corticosteroids within the past 6 months

5. have a history of EGID including EoE

6. younger than 18 years of age