ANAPHYLAXIS CAMPAIGN
Challenges in Food Allergy
Professor Ian Kimber University of Manchester
DEFINITION OF TERMS
ADVERSE REACTIONS TO FOOD
FOOD POISONING FOOD ALLERGY AND INTOLERANCE
IMMUNE MEDIATED ALLERGY
NON IMMUNE MEDIATED INTOLERANCE
THE IMMUNE SYSTEM
Friend or Foe?
SEVERE COMBINED IMMUNODEFICIENCY DISEASE
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.
MOST FOOD ALLERGY IS IgE ANTIBODY MEDIATED
INCREASING PREVALENCE OF IgE ALLERGIES
Asthma prevalence in Europe (children and young adults)
ANTIBODY PRODUCTION
T
P
B help
Differentiation
IgG antibody
IgE ANTIBODY PRODUCTION
P
P
T
B help
Differentiation
IgG antibody
IgE antibody
MAST CELL DEGRANULATION
IgE ANTIBODY PRODUCTION MAST CELL
SENSITISATION
LEUKOTRIENES VASOACTIVE AMINES
and other inflammatory mediators
within minutes of challenge
WHAT FOODS CAUSE ALLERGY?
KIWI FRUIT ALLERGY
2
4
6
8
10
12
Alle
rgy
pu
blic
atio
ns
kiwi fruit introduced to UK diet
first paper published on
kiwi fruit allergy
kiwi fruit recognized as
important allergen
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
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
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
INTRINSIC DIFFERENCES IN ALLERGENIC PROPERTIES
Strongly/commonly allergenic
Weakly/rarely allergenic
PEANUT LETTUCE POTENCY
PERSISTENCE
Commonly life-long
Usually transient
PEANUT COWS’ MILK
IMPORTANT INFLUENCES ON ALLERGENIC ACTIVITY
• SIZE
• FUNCTION
• STABILITY
• SUGARS
• IMMUNOGENICITY
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
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)
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
THE BALANCE BETWEEN ALLERGY AND TOLERANCE
ALLERGY
TOLERANCE
Journal of Allergy and Clinical Immunology 122, 984-991, 2008.
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
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.
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
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
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
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?
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