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?