wheat allergy
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Wheat allergy Presented by Planee Vatanasurkitt,MD., 20110923TRANSCRIPT
WHEAT ALLERGY
Planee Vatanasurkitt,MD
TOPIC OUTLINE
Prevalence Manifestation : children, adult Natural history Wheat allergen Diagnosis Cross-reactivity with grass Processing on allergenicity of wheat
allergen WDEIA: pathogenesis
PREVALENCE
0.4-1 % of children Venter C. incidence of parentally
reported and clinically diagnosed food allergy in the first year of life JACI 2006;117:1118-24
0.3-0.5 % of children 0-14 yr Roehr CC. food allergy and nonallergic
food hypersensitivity in children and adolecent. Clin Exp Allergy 2004:34:1534-41
0.4% in adult Vierk KA. Prevalence of self-reported
food allergy in american adult and use of food label.JACI 2007;119:1504-1510
NATURAL HISTORY OF WHEAT ALLERGY From Johns Hopkins pediatric allergy
clinic 1999-2006 total 5000 children 103 patient had symptomatic reaction
to wheat and positive wheat IgE test result
Keet et al .The natural history of wheat allergy:Ann Allergy Asthma immunol.2009;102:410-15
Keet et al .The natural history of wheat allergy:Ann Allergy Asthma immunol.2009;102:410-15
Keet et al .The natural history of wheat allergy:Ann Allergy Asthma immunol.2009;102:410-15
RATE OF RESOLUTION
age Rate of resolution
4 yrs 29%
8 yrs 56%
12 yrs 65%
Keet et al .The natural history of wheat allergy:Ann Allergy Asthma immunol.2009;102:410-15
PREDICTORS OF PROGNOSIS
Wheat IgE level correlated with resolution of allergy and peak wheat IgE level predict rate of resolution
Peak wheat IgE Median age of tolerance
<20kU/L 31 months
20-49 kU/L 54 months
>50 kU/L 145 months
Keet et al .The natural history of wheat allergy:Ann Allergy Asthma immunol.2009;102:410-15
WHEAT ALLERGY : STUDY
retrospective study ;350 children aged less than 7 yr with food hypersensitivity treated in
the Department of Allergology, Helsinki University Central Hospital, Helsinki, Finland,
between 1992 and 1998, were reviewed to identify patients with wheat hypersensitivity.Kotanie mi-Syrjanen et al. The prognosis of wheat hypersensitivity
:Pediatr Allergy Immunol 2010: 21: e421–e428.
Kotanie mi-Syrjanen et al. The prognosis of wheat hypersensitivity :Pediatr Allergy Immunol 2010: 21: e421–e428.
SENSITIZATION TO WHEAT AND GLIADIN, AND OTHER FOOD
15/21 IgE mediated wheat hypersensitivity had positive SPT reaction to cow’s milk
18/21 had positive SPT to hen’s egg 25/28 wheat allergic children had
challenge proven cow milk allergy Sensitization to giadin is associated
with slower achievement of tolerance and increased risk of asthmaKotanie mi-Syrjanen et al. The prognosis of wheat hypersensitivity
:Pediatr Allergy Immunol 2010: 21: e421–e428.
RISK FACTORS FOR DEVELOPMENT RESPIRATORY ALLERGY AND ASTHMA
62% had become sensitized to birch pollen
68% had symptoms of allergic rhinoconjunctivitis during follow up at median age 4.4 yr
89% of children positive SPT to both wheat and hen egg development allergic rhinitis later in childhood
Kotanie mi-Syrjanen et al. The prognosis of wheat hypersensitivity :Pediatr Allergy Immunol 2010: 21: e421–e428.
RISK FACTORS FOR DEVELOPMENT RESPIRATORY ALLERGY AND ASTHMA
Asthma was diagnosed in 12 [43%] at median age 1.9 yr
Incidence of asthma 64% in gliadin sensitized children comparison with 21% in gliadin-negative children
Kotanie mi-Syrjanen et al. The prognosis of wheat hypersensitivity :Pediatr Allergy Immunol 2010: 21: e421–e428.
WHEAT ALLERGY: A DOUBLE-BLIND,PLACEBO-CONTROLLED STUDY IN ADULTS
27 patients Age 14-60 years History suspected wheat allergy Method : DBPCFC raw and cooked
wheat, SPT, Ig E
JACI 2006;117:433-9
14/27 [52%] had positive result for glass pollen
Most subjects also report food allergy to other fruits and vegetables
13/27 [48%] positive to wheat DBPCFC 38% of challenge positive patients were
grass pollen positive compared with 64% in the challenge negative group
JACI 2006;117:433-9
JACI 2006;117:433-9
JACI 2006;117:433-9
JACI 2006;117:433-9
JACI 2006;117:433-9
WHEAT ALLERGY
Low incidence <1 % presentation : skin > GI > RS Immediate reaction > delayed reaction age of tolerance 6-7 years Associated with development of allergic
rhinoconjunctivitis Wheat allergy does occur in adult patient Sensitivity and specificity of SPT and specific
IgE for wheat in diagnosis of wheat allergy are low
ALLERGEN INVOLVED IN WHEAT ALLERGY Categorized in to four fraction on basis
of solubility Water soluble: albumin Salt soluble : globulin Aqueous alcohol: gliadins Dilute alkali/acid : glutelins
Pastorello EA et al. European patients: alpha-amylase inhibitors , lipid transferproteins and low molecular-weight glutenins. Allergenic molecules recognized by double blind, placebo-controlled food challenge.
Int Arch Allergy Immunol 2007; 144:10 – 22.
Sera of 16 wheat challenge-positive patients and 6 patient with wheat anaphylaxis
Immunobloting of three Osborne’s protein fraction
Pastorello EA et al. European patients: alpha-amylase inhibitors , lipid transferproteins and low molecular-weight glutenins. Allergenic molecules recognized by double blind, placebo-controlled food challenge.
Int Arch Allergy Immunol 2007; 144:10 – 22.
Raw wheat Cooked wheat
Pastorello EA et al. European patients: alpha-amylase inhibitors , lipid transferproteins and low molecular-weight glutenins. Allergenic molecules recognized by double blind, placebo-controlled food challenge.
Int Arch Allergy Immunol 2007; 144:10 – 22.
Albumin/globulin fraction of Raw wheat
Gliadin fraction of raw wheat
Glutenin fraction of raw wheat
Albumin/globulin
Nonspecific LTPAlpha-Amylase/trypsin inhibitorGlobulinPeroxidaseSerpin
Gliadins Alpha-Amylase/trypsin inhibitorGamma-GliadinAlpha-gliadingluteninLMW
Glutenin Alpha-Amylase/trypsin inhibitorpuroindolinTritinLMW gluteninGranule-bound glycogen syntaseBeta- amylase
IN WATER/SALT-SOLUBLE ALBUMIN/GLOBULIN
Most important allergen are amylase/trypsin inhibitor subunit
Responsible for classic food allergy in children with atopic dermatitis and adult
Pastorello EA et al. European patients: alpha-amylase inhibitors , lipid transferproteins and low molecular-weight glutenins. Allergenic molecules recognized by double blind, placebo-controlled food challenge.
Int Arch Allergy Immunol 2007; 144:10 – 22.
IN WATER/ SALT-INSOLUBLE GLUTEN
gliadins are involved in WDEIA, some cases of atopic dermatitis and in anaphylaxis in adults and children.
Among the gliadins, ώ-5 gliadin (Tri a 19)
was identified as a major allergen of WDEIA
JACI 1999; 103 :912 -17
J Dermatol Sci 2003; 33: 99 – 104.
GLIADIN
Four of seven B-cell epitopes of ώ -5 gliadin identified in WDEIA (QQI PQQQ , QQF PQQQ , QQS PEQQ , and QQ SPQQQ ) were found to be dominant
Battais et al. reported that IgE antibodies of patients with WDEIA and classic wheat allergy recognized sequential epitopes of repetitive domains of ώ -5 gliadin.Allergy 2005;60:815-21
J Biol Chem 2004;279:12135-40
GLUTENINS
Glutenins in the water/salt-insoluble fraction are polymeric proteins made up of subunits of HMW and low molecular weight (LMW)
Three B-cell epitopes of HMW glutenin subunits from repetitive domains, QQPG Q, QQPG QGQQ,and QQS GQSGQ, were identified in a minor subgroup of WDEIA
LMW glutenin subunit s are also involved in child and adult wheat immediate allergies , including WDEIA
J Immunol 2005;175:8116-22
NON SPECIFIC LIPID TRANSFER PROTEIN Wheat non specific lipid transfer
protein (nsL TP) (Tri a 14) with a molecular weight of 9 kDa was recently identified as a new wheat allergen in nine out of 22 patients with wheat food allergy by IgE immunoblotting followed by mass spectrometry, and was confirmed to have the biological activity in vivo by a positive SPT with purified wheat LTP
Pastorello EA et al. European patients: alpha-amylase inhibitors , lipid transferproteins and low molecular-weight glutenins. Allergenic molecules recognized by double blind, placebo-controlled food challenge. Int Arch Allergy Immunol 2007; 144:10 – 22.
NON SPECIFIC LIPID TRANSFER PROTEIN 28% of 60 patient with wheat food
allergy shower IgE reaction with purified wheat LTP
Wheat nsLTP has also been reported as an inhalant allergen in baker asthma
Pastorello EA et al. European patients: alpha-amylase inhibitors , lipid transferproteins and low molecular-weight glutenins. Allergenic molecules recognized by double blind, placebo-controlled food challenge.
Int Arch Allergy Immunol 2007; 144:10 – 22.
OTHER
Some studies using proteomic analysis showed that
several other proteins, such as b -amylase, peroxidase, thioredoxin (Tri a 25 ), and serpin (serine protease inhibit or), were also able to bind IgE from patients with wheat food allergy.
Albumin/globulin
Water/salt insoluble gluten
Glutenin Nonspecific lipid transfer protein
Amylase/trypsin inhibitor
Gliadin High molecular weight Low molecular weight
Classic food allergyAtopic dermatitisWDEIA
Classic food allergyWDEIA
Immediated reaction
Inhalant allergen in baker’s asthma
Protein state and route of exposure to gluten structures probably orient pattern of epitope reactivity and wheat food allergy manifestion
CROSS-REACTIVITY OF WHEAT ALLERGENS WITH GRASS
CROSS-REACTIVITY OF WHEAT ALLERGENS WITH GRASS
Jones et al. demonstrated clinically insignificant cross-reactivity between cereals and grasses in children with confirmed wheat allergy by oral challenge in US
Pastorello et al. showed lack of cross-reactivity between α-amylase inhibitor and grass pollen allergen and between nsLTP and grass pollen allergens
JACI1995;96:341-51
Int Arch Allergy Immunol 2007;144:10-22
PROCESSING ON ALLERGENICITY OF WHEAT ALLERGENS
Immunoblotting of cooked wheat
When heating Some patient lost their IgE binding capacity toward LTP
DIAGNOSTIC TEST FOR WHEAT ALLERGY Using CAP system ,PPV less than 75% Poor capacity due to commercial test
reagent are mixture of wheat/salt-soluble wheat protein which lack allergen from insoluble gliadin fraction
Recently the role of ώ-5 gliadin for diagnosis of wheat allergy was highlighted
DIAGNOSTIC TEST FOR WHEAT ALLERGY Maximum efficiency of ώ-5 gliadin for
diagnosis WDEIA was 0.89kUa/l Sensitivity 78% specificity 96%
Matsuo et al sensitivity and specificity of recombinant omega 5 gliadin-specific IgE measurement in WDEIA
Allergy 2008;63:233-36
SENSITIVITY IN 50 JAPANESE WDEIA
Specific IgE to rώ5 gliadin
80%
Specific igE to wheat 48%
Specific IgE to gluten 56%
B cell epitope peptide of ώ5 gliadin
76%
B cell epitope of HMW glutenin
22%
By immunoCAP system
Matsuo et al sensitivity and specificity of recombinant omega 5 gliadin-specific IgE measurement in WDEIA
Allergy 2008;63:233-36
DIAGNOSIS TEST FOR WHEAT ALLERGY
In germany ,US studyMost patient have history of atopic dermatitis
No correlation with level of ώ5 gliadin specific IgE and outcome of oral wheat challenge
Ito et al High concentration of IgE specific to ώ5 gliadin had high risk of failing wheat challege
DIAGNOSIS
In vitro : specific IgE to 5 gliadin in immediate reaction to wheat
In vivo : challenge test, SPT with purified and recombinant wheat allergen
WHEAT-DEPENDENT ,EXERCISE-INDUCED ANAPHYLAXIS IN THAI CHILDREN
Three-day challenge protocol Open challenge for wheat day 1 Exercise challenge test day 2 Exercise challenge test after meal
containing wheat on day 3
OPEN CHALLENGE FOR WHEAT
The challenge protocol started with 1 gram of wheat. The amount was doubled every 30 minutes until a dose of 16 grams of wheat was reached (a cumulative dose of 31 grams)
EXERCISE CHALLENGE
an exercise challenge was performed on a steady-state, motor-driven treadmill with slope and velocities adjusted to achieve 80 percent of the maximum predicted workload for the individual age of the patients.
The exercise was then maintained at this level for 6 minutes.
lung function test was performed before, immediately after and at 3, 5, 10, 15, 20, and 30 minutes after the exercise challenge
EXERCISE CHALLENGE AFTER A MEAL CONTAINING WHEAT
An exercise challenge test was performed within one hour after a meal containing at least 16 grams of wheat
PATHOPHYSIOLOGICAL MECHANISM FOR FOOD DEPENDENT EXERCISE-INDUCED ANAPHYLAXIS
1. Exercise-induced change in plasma osmolarity
2. Alteration in blood pH with exercise3. Tissue transglutaminase activity .IL-6
and exercise4. Redistribution of blood during exercise
and mast cell heterogeneity5. Changes in gut permeability and
exercisePaula Robson-ansley ,George Du Toit.pathophysiology diagnosis and management of exercise-induced anaphylaxisCurrent Opinion in allergy and clinical immunology 2010,10:312-317
EXERCISE-INDUCED CHANGE IN PLASMA OSMOLARITY
Recent research demonstrated that in vitro alteration in osmolarity can increase basophil activation and histamine releasability
Barg et al. food dependent exercised induced anaphylaxisJ Investig Allergol Clin Immunol 2008;18:312-315
EXERCISE-INDUCED CHANGE IN PLASMA OSMOLARITY
Barg et al. performed histamine releasing assays using a range of buffers 280, 340, 450 mOsm in FDEIA ,food allergy and healthy
Demonstrated an increase histamine release in the FDEIA at 340 mOsm but not other group
340 mOsm are pathological and would not be achieved even vigorous exerciseBarg et al. food dependent exercised induced
anaphylaxisJ Investig Allergol Clin Immunol 2008;18:312-315
ALTERATION IN BLOOD PH WITH EXERCISE
Optimal mast cell degranulation occur at a pH 7.0
During sub optimal exercise pH remain the same at rest but during very heavy exercise pH decrease and may be low as 7.0 in the arterial blood
Saeki K.histamine release by inorganic from mast cell granules isoloated by different procedureJpn J pharmacol 1972;22:27-32
Hultman E. acid-base balance during exercised.Exec Sport Sci Rev 1980;8:41-128
TISSUE TRANSGLUTAMINASE ACTIVITY IL-6,EXERCISE
During exercise IL-6 is actively produced within contracting skeletal muscle and central nervous system
IL-6 increase expression of tTG Tissue transglutaminase enzyme
may result in peptide aggregation that leads to increase IgE crosslinking
Palosuo K.transglutaminase-mediated cross linking of o peptic fraction of omega-5 gliadin enhance igE reactivity in wheat-dependent exercise induced anaphylaxis. JACI 2003 .111:1386-1392
REDISTRIBUTION OF BLOOD DURING EXERCISE AND MAST CELL HETEROGENEITY
Exercise –induced redistribution of blood flow away from the viscera to skeletal muscle
Gut tolerated peptide are redistributed to sensitized mast cell inducing EIA
Paula Robson-ansley ,George Du Toit.pathophysiology diagnosis and management of exercise-induced anaphylaxisCurrent Opinion in allergy and clinical immunology 2010,10:312-317
CHANGE IN GUT PERMEABILITY AND EXERCISE
Tight junction in GI tract can become relaxed
Allerginic peptide having greater access to gut associated immune system
Paula Robson-ansley ,George Du Toit.pathophysiology diagnosis and management of exercise-induced anaphylaxisCurrent Opinion in allergy and clinical immunology 2010,10:312-317
MANAGEMENT
If a diagnosis of FDEIA has been made then allergen should be avoid both prior to and after exercise
Suggest a 3h avoidance prior to exercise and 1 h following exercise
Recognition of prodromal manifestation of EIA is important to discontinue exercise at the earliest warning sign
Emergency plan and medication Exercise with a companion who aware of the
conditionPaula Robson-ansley ,George Du Toit.pathophysiology diagnosis and management of exercise-induced anaphylaxisCurrent Opinion in allergy and clinical immunology 2010,10:312-317
SUMMARY
Wheat allergy are low prevalence Important allergen in wheat
:amylase/trypsin inhibitor subunit, ώ-5 gliadin,nsLTP
Manifestation: skin ,GI,RS Diagnosis : challenge , IgE to ώ-5
gliadin in immediated reaction to wheat Treatment : avoid Prognosis : 50 % tolerance in age 6-7
years