Natural History and Genetics of Food Allergy and Related Conditions
Natural History and Genetics of Food Allergy and Related Conditions
Background:

 - About 15 million Americans have a food allergy. Because there are no cures or effective
 prevention or treatment for food allergies, researchers want to learn more about them.

 Objective:

 - To learn more about the causes and effects of food allergy and related conditions.

 Eligibility:

 -  People ages 2 99 who have food allergy and/or a related genetic or other condition

 -  Their relatives

 -  Healthy relatives and volunteers

 Design:

 -  Participants will have at least 3 visits over 1 2 years, and then once a year for up to
 12 years. Each may last a day or longer.

 -  Participants will be screened with medical history, physical exam, and questionnaires.

 -  Participants may have the following:

 -  Blood tests

 -  Allergy skin prick tests: Drops of allergens are placed on the back or arm. The skin is
 scratched under each drop.

 -  Leukapheresis: blood is taken from a needle in one arm, passed through a machine, and
 returned through a needle in the other arm.

 -  X-rays

 -  Esophageal string test: One end of a string is taped to the cheek and the other end is
 packed into a capsule. When the capsule is swallowed, the string unwinds; it is left in
 for at least 1 hour.

 -  EGD and colonoscopy: Biopsies are taken from the gastrointestinal system.

 -  Tiny biopsies of skin

 -  Photographs of the body

 -  Collection of cells through:

 -  Swab of nose, inside of cheek, or skin

 -  Gentle skin scrape

 -  Tape stripping: piece of tape is put on the skin and pulled off.
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 of enrollment for participants who will be seen at
 the NIH CC; be 0 (newborn) to 99 years-old at the time of enrollment for participants
 who will submit mail-in samples or participate in telehealth visits. Only viable
 neonates will be enrolled.

 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)

 4. Have a diagnosis of eosinophilic esophagitis (EoE), or clinical suspicion for EoE as
 determined by the principal investigator (PI) or associate investigators (AIs)

 5. Have a history of atopic dermatitis based on self-report or physician assessment.

 ADDITIONAL INCLUSION CRITERIA FOR UNAFFECTED RELATIVES:

 In addition to the general criteria listed above, unaffected relatives must meet the
 following criteria:

 1. Be a relative of 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 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