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Wheat allergy      <br />PlaneeVatanasurkitt,MD<br />
Topic outline<br />Prevalence<br />Manifestation : children, adult<br />Natural history<br />Wheat allergen<br />Diagnosis...
prevalence<br />0.4-1 % of children <br />Venter C. incidence of parentally reported and clinically diagnosed food allergy...
0.4% in adult <br />Vierk  KA. Prevalence of self-reported food allergy in american adult and use of food label.JACI 2007;...
Natural history of wheat allergy<br />From Johns Hopkins pediatric allergy clinic 1999-2006  total 5000 children<br />103 ...
Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma  immunol.2009;102:410-15<br />
Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma  immunol.2009;102:410-15<br />
Rate of resolution<br />Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma  immunol.2009;102:410-15...
Predictors of prognosis<br />Wheat IgE level correlated with resolution of allergy and peak wheat IgE level predict rate o...
Wheat allergy : study<br />retrospective study ;350 children <br />aged less than 7 yr<br />with food hypersensitivity tre...
Kotaniemi-Syrjanenet al. The prognosis of wheat hypersensitivity<br />:Pediatr Allergy Immunol 2010: 21: e421–e428.<br />
Sensitization to wheat and gliadin, and other food<br />15/21 IgE mediated wheat hypersensitivity  had positive SPT reacti...
Risk factors for development respiratory allergy and asthma<br />62% had become sensitized to birch pollen<br />68% had sy...
Risk factors for development respiratory allergy and asthma<br />Asthma was diagnosed in 12 [43%] at median age 1.9 yr<br ...
Wheat allergy: a double-blind,Placebo-controlled study in adults<br />27 patients<br />Age 14-60 years<br />History suspec...
14/27 [52%] had positive result for glass pollen<br />Most subjects also report food allergy to other fruits and vegetable...
JACI 2006;117:433-9<br />
JACI 2006;117:433-9<br />
JACI 2006;117:433-9<br />
JACI 2006;117:433-9<br />
Wheat allergy<br />Low incidence <1 %<br />presentation : skin  > GI > RS<br />Immediate reaction > delayed reaction<br />...
Allergen involved in wheat allergy<br />Categorized in to four fraction on basis of solubility<br />Water soluble: albumin...
Sera of 16 wheat challenge-positive patients and 6 patient with wheat anaphylaxis<br />Immunobloting of three Osborne’s pr...
Raw wheat<br />Cooked wheat<br />Pastorello EA et al. European patients: alpha-amylase inhibitors , lipid transferproteins...
Albumin/globulin fraction of Raw wheat<br />
Gliadin fraction of raw wheat<br />
Glutenin fraction of raw wheat<br />
In water/salt-soluble albumin/globulin<br />Most important allergen are amylase/trypsin inhibitor subunit<br />Responsible...
In water/ salt-insoluble gluten<br />gliadinsare involved in WDEIA, some cases of atopic dermatitis and in anaphylaxis in ...
Gliadin<br />Four of seven B-cell epitopes of ώ -5 gliadinidentified in WDEIA (QQI PQQQ , QQF PQQQ , QQS PEQQ , and QQ SPQQ...
Glutenins<br />Glutenins in the water/salt-insoluble fraction are polymeric proteins made up of subunits of HMW and low mo...
Non specific lipid transfer protein<br />Wheat non specific lipid transfer protein (nsL TP) (Tri a 14) with a molecular wei...
Non specific lipid transfer protein<br />28% of 60 patient with wheat food allergy shower IgE reaction with purified wheat...
other<br />Some studies <br />using proteomic analysis showed that several other proteins, such as b -amylase, peroxidase,...
Protein state and route of exposure to gluten structures probably orient pattern of epitope reactivity <br />and wheat foo...
Cross-reactivity of wheat allergens with grass <br />
Cross-reactivity of wheat allergens with grass <br />Jones et al. demonstrated clinically insignificant cross-reactivity b...
Processing on allergenicity of wheat allergens<br />
Immunoblotting  of cooked wheat<br />When heating <br />Some patient lost their IgE binding capacity toward LTP<br />
Diagnostic test for wheat allergy<br />Using CAP system ,PPV less than 75%<br />Poor capacity due to commercial test reage...
Diagnostic test for wheat allergy<br />Maximum efficiency of ώ-5 gliadin  for diagnosis WDEIA was 0.89kUa/l<br />Sensitivi...
Sensitivity in 50 Japanese WDEIA<br />By immunoCAP system<br />Matsuo et al sensitivity and specificity of recombinant ome...
Diagnosis test for wheat allergy<br />
diagnosis<br />In vitro : specific IgE to 5 gliadin in immediate reaction to wheat<br />In vivo : challenge test, SPT with...
Wheat-dependent ,Exercise-induced Anaphylaxis in thai children<br />Three-day challenge protocol<br />Open challenge for w...
Open challenge for wheat<br />The challenge protocol started with 1 gram of wheat.  The amount was doubled every 30 minute...
Exercise challenge<br />an exercise challenge was performed on a steady-state, motor-driven treadmill with slope and veloc...
Exercise challenge after a meal containing wheat<br />An exercise challenge test was performed within one hour after a mea...
Pathophysiological mechanism for food dependent exercise-induced anaphylaxis<br />Exercise-induced change in plasma osmola...
Exercise-induced change in plasma osmolarity<br />Recent research demonstrated that in vitro alteration in osmolarity can ...
Exercise-induced change in plasma osmolarity<br />Barg et al. performed histamine releasing assays using  a range of buffe...
Alteration in blood pH with exercise<br />Optimal mast cell degranulation occur at a pH 7.0<br />During sub optimal exerci...
Tissue transglutaminase activity IL-6,exercise<br />During exercise IL-6 is actively produced within contracting skeletal ...
Redistribution of blood during exercise and mast cell heterogeneity<br />Exercise –induced redistribution of blood flow aw...
Change in gut permeability and exercise<br />Tight junction in GI tract can become relaxed<br />Allerginic peptide having ...
management<br />If a diagnosis of FDEIA has been made then allergen should be avoid both prior to and after exercise<br />...
summary<br />Wheat allergy  are low prevalence<br />Important allergen in wheat :amylase/trypsin inhibitor subunit, ώ-5 gl...
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Wheat allergy

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Wheat allergy

Presented by Planee Vatanasurkitt,MD.,

20110923

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Transcript of "Wheat allergy"

  1. 1. Wheat allergy <br />PlaneeVatanasurkitt,MD<br />
  2. 2. Topic outline<br />Prevalence<br />Manifestation : children, adult<br />Natural history<br />Wheat allergen<br />Diagnosis <br />Cross-reactivity with grass<br />Processing on allergenicity of wheat allergen<br />WDEIA: pathogenesis<br />
  3. 3. prevalence<br />0.4-1 % of children <br />Venter C. incidence of parentally reported and clinically diagnosed food allergy in the first year of life JACI 2006;117:1118-24<br />0.3-0.5 % of children 0-14 yr<br />Roehr CC. food allergy and nonallergic food hypersensitivity in children and adolecent. Clin Exp Allergy 2004:34:1534-41<br />
  4. 4. 0.4% in adult <br />Vierk KA. Prevalence of self-reported food allergy in american adult and use of food label.JACI 2007;119:1504-1510<br />
  5. 5. Natural history of wheat allergy<br />From Johns Hopkins pediatric allergy clinic 1999-2006 total 5000 children<br />103 patient had symptomatic reaction to wheat and positive wheat IgE test result<br />Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma immunol.2009;102:410-15<br />
  6. 6. Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma immunol.2009;102:410-15<br />
  7. 7. Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma immunol.2009;102:410-15<br />
  8. 8. Rate of resolution<br />Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma immunol.2009;102:410-15<br />
  9. 9. Predictors of prognosis<br />Wheat IgE level correlated with resolution of allergy and peak wheat IgE level predict rate of resolution<br />Keet et al .The natural history of wheat allergy<br />:Ann Allergy Asthma immunol.2009;102:410-15<br />
  10. 10. Wheat allergy : study<br />retrospective study ;350 children <br />aged less than 7 yr<br />with food hypersensitivity treated in the Department of Allergology, Helsinki University Central Hospital, Helsinki, Finland,<br />between 1992 and 1998, were reviewed to identify patients with wheat hypersensitivity.<br />Kotaniemi-Syrjanenet al. The prognosis of wheat hypersensitivity<br />:Pediatr Allergy Immunol 2010: 21: e421–e428.<br />
  11. 11. Kotaniemi-Syrjanenet al. The prognosis of wheat hypersensitivity<br />:Pediatr Allergy Immunol 2010: 21: e421–e428.<br />
  12. 12. Sensitization to wheat and gliadin, and other food<br />15/21 IgE mediated wheat hypersensitivity had positive SPT reaction to cow’s milk<br />18/21 had positive SPT to hen’s egg<br />25/28 wheat allergic children had challenge proven cow milk allergy<br />Sensitization to giadin is associated with slower achievement of tolerance and increased risk of asthma<br />Kotaniemi-Syrjanenet al. The prognosis of wheat hypersensitivity<br />:Pediatr Allergy Immunol 2010: 21: e421–e428.<br />
  13. 13. Risk factors for development respiratory allergy and asthma<br />62% had become sensitized to birch pollen<br />68% had symptoms of allergic rhinoconjunctivitis during follow up at median age 4.4 yr<br />89% of children positive SPT to both wheat and hen egg development allergic rhinitis later in childhood<br />Kotaniemi-Syrjanenet al. The prognosis of wheat hypersensitivity<br />:Pediatr Allergy Immunol 2010: 21: e421–e428.<br />
  14. 14. Risk factors for development respiratory allergy and asthma<br />Asthma was diagnosed in 12 [43%] at median age 1.9 yr<br />Incidence of asthma 64% in gliadin sensitized children comparison with 21% in gliadin-negative children<br />Kotaniemi-Syrjanenet al. The prognosis of wheat hypersensitivity<br />:Pediatr Allergy Immunol 2010: 21: e421–e428.<br />
  15. 15. Wheat allergy: a double-blind,Placebo-controlled study in adults<br />27 patients<br />Age 14-60 years<br />History suspected wheat allergy<br />Method : DBPCFC raw and cooked wheat, SPT, Ig E <br />JACI 2006;117:433-9<br />
  16. 16. 14/27 [52%] had positive result for glass pollen<br />Most subjects also report food allergy to other fruits and vegetables<br />13/27 [48%] positive to wheat DBPCFC<br />38% of challenge positive patients were grass pollen positive compared with 64% in the challenge negative group<br />JACI 2006;117:433-9<br />
  17. 17. JACI 2006;117:433-9<br />
  18. 18. JACI 2006;117:433-9<br />
  19. 19. JACI 2006;117:433-9<br />
  20. 20. JACI 2006;117:433-9<br />
  21. 21. Wheat allergy<br />Low incidence <1 %<br />presentation : skin > GI > RS<br />Immediate reaction > delayed reaction<br /> age of tolerance 6-7 years<br />Associated with development of allergic rhinoconjunctivitis<br />Wheat allergy does occur in adult patient<br />Sensitivity and specificity of SPT and specific IgE for wheat in diagnosis of wheat allergy are low<br />
  22. 22. Allergen involved in wheat allergy<br />Categorized in to four fraction on basis of solubility<br />Water soluble: albumin<br />Salt soluble : globulin<br />Aqueous alcohol: gliadins<br />Dilute alkali/acid : glutelins<br />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. <br />Int Arch Allergy Immunol 2007; 144:10 – 22.<br />
  23. 23. Sera of 16 wheat challenge-positive patients and 6 patient with wheat anaphylaxis<br />Immunobloting of three Osborne’s protein fraction<br />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. <br />Int Arch Allergy Immunol 2007; 144:10 – 22.<br />
  24. 24. Raw wheat<br />Cooked wheat<br />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. <br />Int Arch Allergy Immunol 2007; 144:10 – 22.<br />
  25. 25. Albumin/globulin fraction of Raw wheat<br />
  26. 26. Gliadin fraction of raw wheat<br />
  27. 27. Glutenin fraction of raw wheat<br />
  28. 28.
  29. 29. In water/salt-soluble albumin/globulin<br />Most important allergen are amylase/trypsin inhibitor subunit<br />Responsible for classic food allergy in children with atopic dermatitis and adult <br />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. <br />Int Arch Allergy Immunol 2007; 144:10 – 22.<br />
  30. 30. In water/ salt-insoluble gluten<br />gliadinsare involved in WDEIA, some cases of atopic dermatitis and in anaphylaxis in adults and children.<br />Among the gliadins, ώ-5 gliadin(Tri a 19) was identified as a major allergen of WDEIA<br />JACI 1999; 103 :912 -17<br />J DermatolSci 2003; 33: 99 – 104.<br />
  31. 31. Gliadin<br />Four of seven B-cell epitopes of ώ -5 gliadinidentified in WDEIA (QQI PQQQ , QQF PQQQ , QQS PEQQ , and QQ SPQQQ ) were found to be dominant <br />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.<br />J BiolChem 2004;279:12135-40<br />Allergy 2005;60:815-21<br />
  32. 32. Glutenins<br />Glutenins in the water/salt-insoluble fraction are polymeric proteins made up of subunits of HMW and low molecular weight (LMW)<br />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<br />LMW glutenin subunit s are also involved in child and adult wheat immediate allergies , including WDEIA<br />J Immunol 2005;175:8116-22<br />
  33. 33. Non specific lipid transfer protein<br />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 IgEimmunoblotting followed by mass spectrometry, and was confirmed to have the biological activity in vivo by a positive SPT with purified wheat LTP<br />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. <br />Int Arch Allergy Immunol 2007; 144:10 – 22.<br />
  34. 34. Non specific lipid transfer protein<br />28% of 60 patient with wheat food allergy shower IgE reaction with purified wheat LTP<br />Wheat nsLTP has also been reported as an inhalant allergen in baker asthma <br />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. <br />Int Arch Allergy Immunol 2007; 144:10 – 22.<br />
  35. 35. other<br />Some studies <br />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.<br />
  36. 36. Protein state and route of exposure to gluten structures probably orient pattern of epitope reactivity <br />and wheat food allergy manifestion<br />
  37. 37. Cross-reactivity of wheat allergens with grass <br />
  38. 38. Cross-reactivity of wheat allergens with grass <br />Jones et al. demonstrated clinically insignificant cross-reactivity between cereals and grasses in children with confirmed wheat allergy by oral challenge in US<br />Pastorello et al. showed lack of cross-reactivity between α-amylase inhibitor and grass pollen allergen and between nsLTP and grass pollen allergens<br />JACI1995;96:341-51<br />Int Arch Allergy Immunol 2007;144:10-22<br />
  39. 39. Processing on allergenicity of wheat allergens<br />
  40. 40. Immunoblotting of cooked wheat<br />When heating <br />Some patient lost their IgE binding capacity toward LTP<br />
  41. 41. Diagnostic test for wheat allergy<br />Using CAP system ,PPV less than 75%<br />Poor capacity due to commercial test reagent are mixture of wheat/salt-soluble wheat protein which lack allergen from insoluble gliadin fraction<br />Recently the role of ώ-5 gliadin for diagnosis of wheat allergy was highlighted<br />
  42. 42. Diagnostic test for wheat allergy<br />Maximum efficiency of ώ-5 gliadin for diagnosis WDEIA was 0.89kUa/l<br />Sensitivity 78% specificity 96%<br />Matsuo et al sensitivity and specificity of recombinant omega 5 gliadin-specific IgE measurement in WDEIA<br />Allergy 2008;63:233-36<br />
  43. 43. Sensitivity in 50 Japanese WDEIA<br />By immunoCAP system<br />Matsuo et al sensitivity and specificity of recombinant omega 5 gliadin-specific IgE measurement in WDEIA<br />Allergy 2008;63:233-36<br />
  44. 44. Diagnosis test for wheat allergy<br />
  45. 45. diagnosis<br />In vitro : specific IgE to 5 gliadin in immediate reaction to wheat<br />In vivo : challenge test, SPT with purified and recombinant wheat allergen<br />
  46. 46. Wheat-dependent ,Exercise-induced Anaphylaxis in thai children<br />Three-day challenge protocol<br />Open challenge for wheat day 1<br />Exercise challenge test day 2<br />Exercise challenge test after meal containing wheat on day 3<br />
  47. 47. Open challenge for wheat<br />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)<br />
  48. 48. Exercise challenge<br />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. <br /> The exercise was then maintained at this level for 6 minutes. <br />lung function test was performed before, immediately after and at 3, 5, 10, 15, 20, and 30 minutes after the exercise challenge<br />
  49. 49. Exercise challenge after a meal containing wheat<br />An exercise challenge test was performed within one hour after a meal containing at least 16 grams of wheat<br />
  50. 50.
  51. 51. Pathophysiological mechanism for food dependent exercise-induced anaphylaxis<br />Exercise-induced change in plasma osmolarity<br />Alteration in blood pH with exercise<br />Tissue transglutaminase activity .IL-6 and exercise<br />Redistribution of blood during exercise and mast cell heterogeneity<br />Changes in gut permeability and exercise<br />Paula Robson-ansley ,George Du Toit.<br />pathophysiology diagnosis and management of exercise-induced anaphylaxis<br />Current Opinion in allergy and clinical immunology 2010,10:312-317<br />
  52. 52. Exercise-induced change in plasma osmolarity<br />Recent research demonstrated that in vitro alteration in osmolarity can increase basophil activation and histamine releasability<br />Barg et al. food dependent exercised induced anaphylaxis<br />J InvestigAllergolClinImmunol 2008;18:312-315<br />
  53. 53. Exercise-induced change in plasma osmolarity<br />Barg et al. performed histamine releasing assays using a range of buffers 280, 340, 450 mOsm in FDEIA ,food allergy and healthy<br />Demonstrated an increase histamine release in the FDEIA at 340 mOsm but not other group<br />340 mOsm are pathological and would not be achieved even vigorous exercise<br />Barg et al. food dependent exercised induced anaphylaxis<br />J InvestigAllergolClinImmunol 2008;18:312-315<br />
  54. 54. Alteration in blood pH with exercise<br />Optimal mast cell degranulation occur at a pH 7.0<br />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<br />Saeki K.histamine release by inorganic from mast cell granules isoloated by different procedureJpn J pharmacol 1972;22:27-32<br />Hultman E. acid-base balance during exercised.Exec Sport Sci Rev 1980;8:41-128<br />
  55. 55. Tissue transglutaminase activity IL-6,exercise<br />During exercise IL-6 is actively produced within contracting skeletal muscle and central nervous system<br />IL-6 increase expression of tTG<br />Tissue transglutaminase enzyme may result in peptide aggregation that leads to increase IgEcrosslinking<br />PalosuoK.transglutaminase-mediated cross linking of o peptic fraction of omega-5 gliadin enhance igE<br />reactivity in wheat-dependent exercise induced anaphylaxis. JACI 2003 .111:1386-1392<br />
  56. 56. Redistribution of blood during exercise and mast cell heterogeneity<br />Exercise –induced redistribution of blood flow away from the viscera to skeletal muscle<br />Gut tolerated peptide are redistributed to sensitized mast cell inducing EIA<br />Paula Robson-ansley ,George Du Toit.<br />pathophysiology diagnosis and management of exercise-induced anaphylaxis<br />Current Opinion in allergy and clinical immunology 2010,10:312-317<br />
  57. 57. Change in gut permeability and exercise<br />Tight junction in GI tract can become relaxed<br />Allerginic peptide having greater access to gut associated immune system <br />Paula Robson-ansley ,George Du Toit.<br />pathophysiology diagnosis and management of exercise-induced anaphylaxis<br />Current Opinion in allergy and clinical immunology 2010,10:312-317<br />
  58. 58. management<br />If a diagnosis of FDEIA has been made then allergen should be avoid both prior to and after exercise<br />Suggest a 3h avoidance prior to exercise and 1 h following exercise<br />Recognition of prodromal manifestation of EIA is important to discontinue exercise at the earliest warning sign<br />Emergency plan and medication<br />Exercise with a companion who aware of the condition<br />Paula Robson-ansley ,George Du Toit.<br />pathophysiology diagnosis and management of exercise-induced anaphylaxis<br />Current Opinion in allergy and clinical immunology 2010,10:312-317<br />
  59. 59. summary<br />Wheat allergy are low prevalence<br />Important allergen in wheat :amylase/trypsin inhibitor subunit, ώ-5 gliadin,nsLTP<br />Manifestation: skin ,GI,RS <br />Diagnosis : challenge , IgE to ώ-5 gliadin in immediated reaction to wheat<br />Treatment : avoid<br />Prognosis : 50 % tolerance in age 6-7 years <br />
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