This document discusses food allergies and challenges in understanding them. It defines key terms like food allergy, intolerance, and anaphylaxis. It explores factors that determine susceptibility to food allergies like inherent and acquired susceptibility, conditions of exposure, the nature of proteins, and allergic sensitization. Studies on peanut allergy are discussed that examine how dietary vs skin exposure and other intrinsic and extrinsic factors can promote or prevent allergic responses. Ongoing research aims to better understand what makes proteins allergenic and drives differences in individual susceptibility to help address the big challenges in food allergy.

1. ANAPHYLAXIS CAMPAIGN
Challenges in Food Allergy
Professor Ian Kimber
University of Manchester

2. DEFINITION OF TERMS
ADVERSE REACTIONS TO FOOD
FOOD POISONING FOOD ALLERGY AND INTOLERANCE
IMMUNE MEDIATED
ALLERGY
NON IMMUNE MEDIATED
INTOLERANCE

3. THE IMMUNE SYSTEM
Friend or Foe?
SEVERE COMBINED IMMUNODEFICIENCY DISEASE

4. FOOD ALLERGY
ALLERGY - The adverse health effects that may
result from the stimulation of an immune
response.
FOOD ALLERGY - Adverse health effects* that are
caused by an allergic reaction to food
proteins encountered in the diet.
* rash, swelling, nausea, vomiting, asthma, anaphylaxis.

5. MOST FOOD ALLERGY IS IgE ANTIBODY
MEDIATED
INCREASING PREVALENCE OF IgE ALLERGIES
Asthma prevalence in Europe
(children and young adults)

6. ANTIBODY PRODUCTION
T
P
B
help
Differentiation
IgG antibody

7. IgE ANTIBODY PRODUCTION
P
P
T
B
help
Differentiation
IgG antibody
IgE antibody

8. MAST CELL DEGRANULATION
IgE ANTIBODY
PRODUCTION MAST CELL
SENSITISATION
LEUKOTRIENES
VASOACTIVE AMINES
and other inflammatory
mediators
within minutes of challenge

9. WHAT FOODS CAUSE ALLERGY?

10. KIWI FRUIT ALLERGY
2
4
6
8
10
12
Allergypublications
kiwi fruit
introduced
to UK diet
first paper
published on
kiwi fruit
allergy
kiwi fruit
recognized as
important allergen

11. WHY HAS THERE BEEN AN INCREASE IN THE
PREVALENCE OF ATOPIC ALLERGY - INCLUDING
FOOD ALLERGY?
5-7% children, 2% adults
Changes in the gene
pool
Altered patterns
of exposure
(chemicals,
pollutants)
The hygiene
hypothesis

12. WHAT FACTORS DETERMINE SUSCEPTIBILITY TO
FOOD ALLERGY
INHERENT
INDIVIDUAL
SUSCEPTIBILITY
Inherited
Acquired
Extrinsic Factors
CONDITIONS OF EXPOSURE
Extent
Frequency
Route
Age
NATURE OF PROTEIN
Intrinsic allergenic potential
Stability
ALLERGIC SENSITISATION

13. WHAT FACTORS DETERMINE SUSCEPTIBILITY TO
FOOD ALLERGY
INHERENT
INDIVIDUAL
SUSCEPTIBILITY
Inherited
Acquired
Extrinsic Factors
CONDITIONS OF EXPOSURE
Extent
Frequency
Route
Age
NATURE OF PROTEIN
Intrinsic allergenic potential
Stability
ALLERGIC SENSITISATION

14. INTRINSIC DIFFERENCES IN ALLERGENIC
PROPERTIES
Strongly/commonly
allergenic
Weakly/rarely
allergenic
PEANUT LETTUCEPOTENCY
PERSISTENCE
Commonly
life-long
Usually
transient
PEANUT COWS’ MILK

15. IMPORTANT INFLUENCES ON
ALLERGENIC ACTIVITY
• SIZE
• FUNCTION
• STABILITY
• SUGARS
• IMMUNOGENICITY

16. WHAT FACTORS DETERMINE SUSCEPTIBILITY TO
FOOD ALLERGY
INHERENT
INDIVIDUAL
SUSCEPTIBILITY
Inherited
Acquired
Extrinsic Factors
CONDITIONS OF EXPOSURE
Extent
Frequency
Route
Age
NATURE OF PROTEIN
Intrinsic allergenic potential
Stability
ALLERGIC SENSITISATION

17. DIETARY EXPOSURE – OR VIA THE SKIN?
• High levels of environmental exposure to peanut
promotes sensitisation (Fox et al., 2008)
• Impaired skin barrier function is associated with
peanut allergy (Brown et al., 2011)
• Skin homing lymphocytes predominate in peanut
allergy (Chan et al., 2012)
• Peanut protein spreads easily throughout the home
and is resistant to cleaning (Brough et al., 2013a)
• Household peanut dust is immunologically active
(Brough et al., 2013b)

18. COMMITTEE ON TOXICITY OF CHEMCIALS IN
FOOD CONSUMER PRODUCTS AND THE
ENVIRONMENT (COT) 1998
Mothers who are atopic (or where there is an atopic
background) may wish to avoid eating peanuts or
peanut products during pregnancy and lactation

19. THE BALANCE BETWEEN ALLERGY AND TOLERANCE
ALLERGY
TOLERANCE

20. Journal of Allergy and Clinical Immunology 122, 984-991, 2008.

21. A NOVEL HYPOTHESIS
•Early dietary exposure to potential allergenic foods
facilitates the development of immunological
tolerance
•Skin exposure to allergenic food proteins promotes
the development of sensitisation

22. LEAP (Learning Early About Peanut Allergies)
The primary aim of the LEAP
Study is to assess whether
oral administration of a
peanut-containing snack can
induce tolerance in children
at high risk for peanut allergy.
The LEAP Study Team: Monica Basting, Charlotte Stedman, Muhsinah Adam, Richard Cleaver, Louise
Coverdale, Amy Nixon, George du Toit, Catherine Clarke, Una O’Dwyer-Leeson and Alicia Parr.

23. The primary aim of the EAT Study is
to assess whether the introduction
of allergenic foods from 3 months of
age, alongside continued
breastfeeding, results in a reduced
prevalence of IgE-mediated food
allergy by 3 years of age.
EAT (Enquiring About Tolerance)
Michael Perkin, Gideon Lack and
Kirsty Logan

24. WHAT FACTORS DETERMINE SUSCEPTIBILITY TO
FOOD ALLERGY
INHERENT
INDIVIDUAL
SUSCEPTIBILITY
Inherited
Acquired
Extrinsic Factors
CONDITIONS OF EXPOSURE
Extent
Frequency
Route
Age
NATURE OF PROTEIN
Intrinsic allergenic potential
Stability
ALLERGIC SENSITISATION

25. Objectives
• Establish a dose-distribution curve for
peanut threshold in a UK peanut
allergic population of adults
• Model the variability of challenge
thresholds over time within individuals,
as a result of repeat challenges
• Examine how these extrinsic factors
shift the dose response curve:
– Exercise
– Stress through sleep deprivation

26. THE BIG CHALLENGES/QUESTIONS
• What makes a protein an allergen?
• What drives inter-individual differences in
susceptibility to food allergy?
• What routes of exposure are relevant for the
acquisition of sensitisation?
• What factors influence the severity of food
allergic reactions?
• Why do some adults develop allergy to foods
that they have tolerated for years?