Antonella Muraro

Referral Centre for Food Allergy Diagnosis and Treatment

Department of Pediatrics, University of Padua

Padua, Italy

muraro@centroallergiealimentari.eu

ALLERGY SCHOOL

Investigating allergic effects on environmental exposure

BRINDISI ( Italy)July 2-5 th, 2014

Food Allergy

FOOD ALLERGY

ADVERSE HEALTH EFFECT ARISING FROM

A SPECIFIC IMMUNE RESPONSE THAT OCCURS REPRODUCIBLY

ON EXPOSURE TO A GIVEN FOOD

NIH-NIAID Food Allergy Guidelines JACI 2011

2 MAIN GROUPS ACCORDING TO THE

MECHANISMS

- IMMUNOLOGICAL (IgE/non IgE) =FOOD ALLERGY

- NON IMMUNOLOGICAL = INTOLERANCE

enzimatic (lactose intolerance)

toxic ( sgombroid syndrome)

pharmacologic

ADVERSE REACTIONS TO FOODS

Outline

Epidemiology

Patient’s diversity : phenotypes

Pollen Food Allergy

Need for individualized therapy

Burden of Food Allergy

• Prevalence:– 3 million school age children (3.9%)

– 18% increase since 1997

Branum 2009 Pediatrics. 124:1549-55

• 7 most common food allergens in Western countries.– Milk, egg, peanut, tree nuts, shellfish, soy, wheat

• Peanut allergy– Prevalence ~1%

– Most common cause of anaphylaxis in children presenting to the ED

– Most common cause of fatal food anaphylaxis

• Standard of care– Avoidance of only foods appropriately diagnosed

– Self-injectable epinephrine/antihistamines

Vander Leek, J Peds 2000

Bock, J Allergy Clin Immunol 2007

EAACI GUIDELIINES 2014

Burden of Food Allergy

Epidemiology (i)

Burden of Food Allergy

Epidemiology (ii)

• Reported increase in severe allergic

reactions from food

– Food-induced anaphylaxis is a leading cause

of outpatient anaphylaxis

– Food-related anaphylaxis increased 13% per

year in a 12-year period

– Food-induced anaphylaxis admissions have

increased in the UK (1990-2004)

– in Australia (1993-2003)

1Webb Ann Allergy 2006, 2Sampson Pediatrics 2003, 3Novembre Pediatrics 1998, 4Bock JACI 2001, 5Mehl Allergy 2005, 6Poulos JACI 2007, 7Gupta Thorax 2007

Patients diversity

SKINGUTRESPIRATORY TRACT

SINGLE OR ASSOCIATED MANIFESTATIONS

SYSTEMIC MANIFESTATIONS

- Urticaria/angioedema- Atopic Dermatitis- Gastroenteropathies- Rhinitis- Asthma

Anaphylaxis

FOOD ALLERGYClinical manifestations

EAACI Task Force on Nomenclature

FOOD HYPERSENSITIVITY

FOOD ALLERGYNON ALLERGIC

HYPERSENSITIVITY

IgE-MEDIATED FOOD ALLERGY

NON IgE-MEDIATED FOOD ALLERGY

FOOD ALLERGY

Allergy, 2001; 56: 813J Allergy Clin Immunol 2004 113;832-6

MixedIgE & nonIgE

IgE Non-IgE

Immediate vomiting, diarrhea, urticaria, respiratory symptomsOral allergy syndrome

Eosinophilic Allergic Esophagitis

Eosinophilic Allergic Gastritis

Eosinophilic Allergic Gastroenterocolitis

Atopic Dermatitis

Food Enterocolitis

Food Proctitis

Food Enteropathy

Atopic dermatitis

Heiner Syndrome

Celiac disease

Sampson HA, et al J Pediatr Gastroenterol Nutrit 2000; 30: 587-594

FOOD ALLERGY CLINICAL MANIFESTATIONS

Does one size fit all?

FOOD ALLERGY Phenotypes

Early v’s late DiseaseSensitization v’s Clinical reactivity

Mild v’s Severe

Persistent v’s Transient

Food Allergy Phenotypes

Early v’s late onset

Pollen Food Allergy

Patient’s diversity (i)Symptoms:

Coexistence of immediate IgE mediated with late non IgE mediated.

Severity:Mild v’s Severe

Cow’s milk: baked-milk tolerant children have milder symptoms than non tolerant

Egg: Baked-egg tolerant children had a low incidence of severe reactions and low egg specific IgE levels

Peanut: tolerant patients had smaller size and lower specific IgE values

•TIMING IN ONSET OF SENSITIZATION

EARLY v’s LATE

•TIMING IN ACHIEVING TOLERANCE

Transient v’s Persistent

Patient’s diversity (ii)

Patients’ diversity (iii)

1

2

Heating

MI

IM

K

LLI

M

KM

I KL

L

K

Effect of Heating on Milk Proteins

LLI

M

KM

I

Nowak-Wegrzyn A: EAACI Food Allergy and Anaphylaxis Meeting- FAAM 2011

Majority of children outgrow milk or egg within first 6 years of life

- children who “outgrow” milk / egg allergy have IgE directed primarily at conformational epitopes

Patients’ diversity (iv)

Role of “informative” Epitopes

– Epitope recognition correlates with peanut allergy severity

– Patient with milk allergy and milk tolerance have different epitope recognition patterns

– Certain milk IgE epitopes can be used as candidate biomarkers to predict the development of tolerance to milk (epitope diversity)

Nowak-Wegrzyn A et al JACI 2008Wang J et al JACI 2010

IgE diversity corresponds to different phenotypes of milk allergy

IgE affinity correlates to different phenotypes of milk & egg allergy:

Role of Informative Epitopes

Patient Diversity (v)How to Identify groups of patients homogeneous

FOR:

• clinical symptoms

• reaction features

• Epitopes Recognition

How to define the Allergic Profile ?

FOR: • Risk of Severe Reactions

•Prognosis

•Tailored treatment

Role ofComponent-Resolved Diagnostics

(CRD)• CRD have been introduced in

order to increase the probabilityof

–True Food Allergy diagnosis

– Identify patients at high risk of reactions

– Identify patients more prone to persistent disease

Hansen et al. J Allergy Clin Immunol. 2009 May;123(5):1134-41, 1141.e1-3.

Suspicion of egg allergyIs it allergy? Risk for severe reactions?

Test with ImmunoCAP AllergenEgg White (f1) + Ovomucoid (f233)

Egg White: neg

Ovomucoid: neg

Egg White: posOvomucoid: neg

Egg White: pos

Ovomucoid: pos

Low risk for

Clinical Reactions

to eggAbsence of IgE antibodies to

ovomucoid indicates tolerance to ingestion of hard-boiled and egg

in baked cakes

Increase risk for

persistent egg

allergy

Mittag JACI 2004, Ballmer-Weber JACI 2007

Kleine-Tebbe JACI 2002, Treudler JInvACI2008

Van Zuuren Allergy 2010, Kosma Acta Pediatr 2011 Holzhauser JACI 2009

Risk for clinical

reactions to egg High risk for clinical

reactions to egg

Suspicion of soy allergyIs it allergy? Risk for severe reactions?

Test with ImmunoCAP AllergenSoybean (f14) + Gly m 4 + Gly m 5/Gly m 6

Soybean: neg

Gly m 4: neg

Gly m 5/Gly m 6: neg

Soybean: pos or

neg

Gly m 4: pos

Gly m 5/Gly m 6: neg

Soybean: pos

Gly m 4: pos or neg

Gly m 5/Gly m 6:

pos

Low risk for

reactions to soy

If patient is pollen-allergic:

Risk for reactions to soy

- predominantly OASbut sometimes severe

Risk for severe

reactions to soy

Mittag JACI 2004, Ballmer-Weber JACI 2007

Kleine-Tebbe JACI 2002, Treudler JInvACI2008

Van Zuuren Allergy 2010, Kosma Acta Pediatr 2011 Holzhauser JACI 2009

Pollen Food Allergy

Profilins

• Sensitisation observed in

pollen allergic patients

• BP<GP

• Monosensitised only in GP

• Pollen allergy preceeds the

fruit allergy

• OAS > 90%

20-75%

13-56% ms

13%

4% ms

19-50%

0-25% ms

15-74%

0-5% ms

PR-10 - Bet v 1 family

• Frequency related to BP

exposure

• BP allergy preceeds the

fruit allergy

• OAS > 90%

0-13%3%

0-91%

0% ms

0-67% ms

92-100%

26-86% ms

Lipid Transfer Protein –LTP

47-100%

44-100% ms

97%

84%ms

13-100%

0-3%

History suggestive of

pollen-food syndrome

Confirmed by SPT

with fresh

material and/or specific IgE

Not confirmed by SPT with fresh

material and/or specific IgE

Oral Challenge

Clinical Features Clinical Features

OAS Systemic Reactions

Both Labile and stable

allergens are suspect

IgE to Bet v 1Positive IgE to Bet v1- 2 Pos

Stable Allergen are suspect

IgE to LPT positiveIgE to seed storage

protein positive

Sensitization

To Bet v1-like

Allergens

Sensitization to both

Bet v1-like allergens and profilin

NO ORAL CHALLENGE NO ORAL CHALLENGE

NO ADRENALINENO ADRENALINE

Sensitization

To LTP (Pru p 3)

Evaluate for potential

cross-reactivities

NO ORAL CHALLENGE

CARRY ADRENALINE

Sensitization to

Storage Protein

Evaluate for potential

Cross-reactivities

NO ORAL CHALLENGE

CARRY ADRENALINE

POLLEN FOOD ALLERGY

Asero R. et al Int.Arch.Allergy Immunol 2005Bohle B, Allergy 2007

Need for

individualized therapy

Individualized treatment (i)

Age

Type and severity of symptoms

Type of allergen

Multiple food allergies

Level of food specific IgE , recombinant

allergens profile and epitope affinity

IS ESSENTIAL IN APPROPRIATE MANAGEMENT

IDENTIFYING the clinical profileof the food allergic patient with regard to:

Individualized Treatment (ii) Future Directions

• Identify environmental factors affecting the development of food allergy

• Develop biomarkers for identifying phenotypes mainly for severe reactors

• Develop diagnostic tests to correctly identify the phenotype of food allergy: transient-permanent to select patients for IT

•

• Molecular approach in order to optimize

opportunities to achieve hypoallergenicity of the extract