Wheat dependent exercise-induced anaphylaxis
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Wheat dependent exercise-induced anaphylaxis Presented by Amornrat Prasertcharoensuk, MD. November03, 2017
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Wheat dependent exercise-induced anaphylaxis
- 2. Food-dependent exercise-induced anaphylaxis ( FDEIA) âĒ First reported in 1979 triggered by a combination of shellfish ingestion and exercise . âĒ FDEIA is IgE mediated; classical symptoms of type 1 hypersensitivity and serum-specific IgE (ssIgE) to culprit allergens are detectable . âĒ Time between meal and exercise is usually between 30 and 120 min , and the duration of exercise before the onset of symptoms last 10-50 min âĒ Causative foods shellfish, wheat products, vegetables, fruits, nuts,egg,mushrooms,corn, garlic,pork, beef,rice,and cows milk Gabriel K. Wong & Mamidipudi T. Krishna, Curr Allergy Asthma Rep (2013) 13:639â644
- 3. âĒ Triggered by wheat ingestion only together with cofactors such as physical activity Wheat-dependent exercise-induced anaphylaxis (WDEIA
- 4. Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced AnaphylaxisâImportance of Omega-5 Gliadin and HMW-Glutenin as Causative Antigens for Wheat-Dependent Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498 Trigger factors in FDEIA
- 5. Schematic figures of food allergen absorption in gastrointestinal tract in the patients with FDEIA A: Ingested foods are digested in the intestine, and no immunoreactive allergens entered into circulation. B: Exercise and/or aspirin enhance absorption of undigested immunoreactive allergens into circulation Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced AnaphylaxisâImportance of Omega-5 Gliadin and HMW-Glutenin as Causative Antigens for Wheat-Dependent Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498
- 6. Overview about WheatOverview about wheat uca Elli, Federica Branchi, Carolina Tomba, Diagnosis of gluten related disorders: Celiac disease, wheat allergy and non-celiac gluten sensitivity
- 7. Gregory J. Tanner, journal of the American Society of Brewing Chemists · February 2014
- 8. Wheat protein Gliadins and glutenins have extremely imbalanced amino acid compositions with high proportions of glutamine (32â53 mol-%) and proline (11â29 mol-%) and low contents (< 2 mol-%) of lysine, methionine, and tryptophan
- 9. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap ,Allergology International Vol 61, No4, 2012
- 10. A. S. Tatham and P. R. Shewryw , Allergens in wheat and related cereals , Clinical and Experimental Allergy, 38, 1712â1726
- 11. Overview about wheat Kathrin Schalk, Barbara Lexhaller Isolation and characterization of gluten protein types from wheat, rye, barley and oats, February 24, 2017
- 12. K. A. Scherf1, K. Brockow,wheat-dependent exercise â induced anaphylaxis , Clinical & Experimental Allergy, 46, 10â20 Wheat
- 13. Allergen Heimo Breiteneder, PhD, and Christian Radauer, PhD, J ALLERGY CLIN IMMUNOL MAY 2004
- 14. Rye g-70 and g-35 secalins and barley g-3 hordein cross-react with v-5 gliadin, a major allergen in wheat-dependent, exercise-induced anaphylaxis , K. PALOSUO*â , H. ALENIUSâ âĄ, E. VARJONEN*, N. KALKKINEN§ and T. REUNALA*Âķ
- 15. âĒ Bakersâ asthma, inhalation of flour and dust during grain processing. group of inhibitors of a-amylase (also called chloroform methanol soluble, or CM, proteins) are the major components responsible for this syndrome. âĒ Wheat-dependent exercise-induced anaphylaxis (WDEIA), with the o5-gliadins (part of the gluten protein fraction) major group of proteins which are responsible. âĒ Other forms of food allergy have also been reported, with the proteins responsible including gluten proteins, CM proteins and non-specific lipid transfer proteins Wheat allergens A. S. Tatham and P. R. Shewryw , Allergens in wheat and related cereals , Clinical and Experimental Allergy, 38, 1712â1726
- 16. Protein epitopes identified as associated with associated with WDEIA K. A. Scherf1, K. Brockow,wheat-dependent exercise â induced anaphylaxis , Clinical & Experimental Allergy, 46, 10â20
- 17. âĒ When IgE binding epitopes were investigated using sera of WDEIA patients, âĒ four epitopes consisting seven amino acids, QQIPQQQ, QQFPQQQ, QQSPEQQ and QQSPQQQ, were found to be dominant epitopes in omega-5 gliadin, âĒ and three epitopes QQPGQ, QQPGQGQQ and QQSGQGQ were identified in HMW glutenin. âĒ Mutational analysis of the QQIPQQQ and QQFPQQQ peptides indicated that five common amino acids at position 1 (Q), 4 (P), 5 (Q), 6 (Q) and 7 (Q) were critical for IgE-binding in omega-5 gliadin CAUSATIVE FOODS AND ALLERGENS RESPONSIBLE FOR WDEIA Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced AnaphylaxisâImportance of Omega-5 Gliadin and HMW-Glutenin as Causative Antigens for Wheat-Dependent Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498
- 18. âĒ Symptoms of WDEIA are usually elicited by physical activity one to four hours after wheat intake âĒ The frequency of WDEIA events varies from patient to patient and ranges from a singular episode to multiple episodes . âĒ The clinical manifestations and severity of allergic reactions from urticaria to anaphylaxis also vary Clinical features K. A. Scherf1, K. Brockow,wheat-dependent exercise â induced anaphylaxis , Clinical & Experimental Allergy, 46, 10â20
- 19. K. A. Scherf1, K. Brockow,wheat-dependent exercise â induced anaphylaxis , Clinical & Experimental Allergy, 46, 10â20 IgE antibody levels
- 20. âĒ In conclusion, omega5-gliadin(Tri a 19 ) and HMW-GS appear to be the major allergens in WDEIA. However, other types of gluten proteins such as a/b- and c-gliadins and LMWGS also can sensitize WDEIA patients. âĒ Case report 9-kDa wheat lipid transfer protein (LTP) (Tri a 14 ) can causative allergen . Causative proteins in WDEIA Ann Allergy Asthma 112(2014) 383-394
- 21. âĒ Exercise : up-regulates intestinal resulting in increased amounts of food antigens in the circulating blood. : enhances the degranulation of mast cells in combination with IgE cross-linking through an unknown mechanism. âĒ Aspirin : damage to the tight junctions in the gastrointestinal mucosa. : degranulation of mast cells and accelerate histamine release via increased Syk kinase activation : PGE 1 may suppress allergen absorption Cofactors
- 23. Cellular and molecular, Abbas 7th edition
- 24. âĒ Route of allergen sensitization : gastrointestinal tract , skin âĒ TG2 may become activated during exercise, which results in conjugates between wheat peptides and TG2 followed by IgE binding âĒ Exercise mobilizes and activates immune cells from gut-associated depots stimulating pro-inflammatory responses that are normally countered by anti-inflammatory responses âĒ Noradrenaline may be involved in the onset of WDEIA, because it selectively inhibits T helper 1 (Th1) functions while favouring Th2 and humoral responses, or acts directly on both cellular and humoral immunity Pathomechanism
- 27. Humoral and Cellular responses
- 28. Humoral and Cellular responses
- 29. âĒ Elevated levels of IgE antibodies to CGE and purified Omega-5 Gliadin . âĒ IgA levels,especially to omega-5 gliadin ,were significantly elevated in the patients . âĒ IgA is the most predominant immunoglobulin at mucosal surfaces, where it is involved in protection against microorganism. âĒ Level of IL-10 mRNA significant lower in patients âĒ IL-10 can inhibit several activation and effector function of T cells, monocytes and macrophages . Humoral and Cellular responses
- 30. Siiri E. Iismaa et al. Physiol Rev 2009;89:991-1023 ÂĐ2009 by American Physiological Society Adaptive and innate immune responses to gluten in the gut.
- 31. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap ,Allergology International Vol 61, No4, 2012 Hydrolyzed wheat Protein in Soap
- 32. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap ,Allergology International Vol 61, No4, 2012
- 33. Yuko Chinukiand Eishin Morita ,Wheat-Dependent Exercise-Induced Anaphylaxis Sensitized with Hydrolyzed Wheat Protein in Soap ,Allergology International Vol 61, No4, 2012
- 34. âĒ All allergy history Data , all factors relating âĒ Diagnostic tools : - in vivo tests such as SPT and provocation tests - in vitro tests including basophil activation test (BAT) ,histamine release test (HRT) and wheat-specific IgE testing Diagnosis SPT using gluten had a sensitivity of 100% and a specificity of 96% Specific igE antibodies to omega-5 gliadin sensitivity (78%-82%)and specificity 100% for patients with WDEIA. Knut Brockow, MD,a Daniel Kneissl,a Luzia Valentini, PhD , J ALLERGY CLIN IMMUNOLAPRIL 2015
- 35. antihistamines and leukotriene antagonists was stopped 3 days . Aspirin (10 mg/kg, maximum500 mg) and the suspected food(s) were administered 90 and 60 min before exercise. 200â400 g Udon noodle (5.2â10.4 g wheat protein), 40â100 g shrimp, or one whole apple. The exercise was started at 2.1 W/kg, and increased up to 3 or 4 W/kg, and was conducted for 6 min or more according to the patientsâ athletic abilities, as the level of exertion can influence the test results . The target heart rate was >160 beats/min.
- 36. Challenge tests for WDEIA âĒ Wheat products included noodles, bread or pasta containing 60-135 g of wheat flour. âĒ Thirty minutes after wheat ingestion, exercise was performed using a treadmill for 15-20 min. âĒ Aspirin (500 mg) was administrated 30 min prior to wheat ingestion. âĒ A positive test was determined if allergic symptoms such as wheals and or anaphylaxis were observed Kunie Kohno1, Hiroaki Matsuo2, Hitoshi Takahashi ,Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis , Allergology International. 2013;62:229-238 Challenge test
- 37. Kunie Kohno1, Hiroaki Matsuo2, Hitoshi Takahashi ,Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis , Allergology International. 2013;62:229-238
- 38. Kunie Kohno1, Hiroaki Matsuo2, Hitoshi Takahashi ,Serum Gliadin Monitoring Extracts Patients with False Negative Results in Challenge Tests for the Diagnosis of Wheat-Dependent Exercise-Induced Anaphylaxis , Allergology International. 2013;62:229-238
- 40. The challenge-confirmed sensitivity and specificity of gluten skin prick tests was 100% and 96%, respectively. Conclusion: Oral challenge with gluten alone or along with ASA and alcohol is a sensitive and specific test for the diagnosis of WDEIA. Exercise is not an essential trigger for the onset of symptoms in patients with WDEIA.
- 41. Eishin Morita1, Hiroaki Matsuo, Food-Dependent Exercise-Induced AnaphylaxisâImportance of Omega-5 Gliadin and HMW-Glutenin as Causative Antigens for Wheat-Dependent Exercise-Induced Anaphylaxis, Allergology International. 2009;58:493-498 IgE measurement in WDEIA and AD
- 42. âĒ Acute management - immediate termination of physical effort - Pharmaceutics such as Adrenaline , Antihistamine âĒ Prevent further episode of WDEIA -education and how to use adrenaline autoinjectors. -written anaphylaxis management plan as well as dietary counselling - classical recommendation of refraining from exercise for 4-6 h after wheat intake may be insufficient because unexpected exercise,NSAIDs . - a gluten â free diet recommended need to avoid wheat only or other gluten- containing cereals . TREATMENT OF WDEIA K. A. Scherf1, K. Brockow,wheat-dependent exercise â induced anaphylaxis , Clinical & Experimental Allergy, 46, 10â20
- 43. www.pantip.com
- 45. āļāļēāļŦāļēāļĢāļāļĩāđāļāļēāļāđāļĄāđāđāļāđ âĒ āļāļāļĄāļāļąāļ āđāļāđāļāļāļĢāļĩāđ āđāļāđāļ āļāļļāđāļāļāļĩāđāļāļēāļĒ āđāļāļĢāļāđāļāļĨ āļāļīāļāļāđāļē āļĨāļēāļāļēāļāļāđāļē āļāļ°āļŦāļĄāļĩāđ āđāļāļĩāđāļĒāļ§ āļāļēāļĨāļēāđāļāļē āļāļēāļāđāļāļāđāļāđ āļāļēāļŦāļēāļĢāļāļļāļāđāļāđāļ āļāļāļāļāļĩāđāđāļāđāđāļāđāļāļŠāļēāļĨāļĩ āļāļēāļŠāļāđāļē āļĄāļąāļāļāļ°āđāļĢāļāļĩ āļŠāļāļēāđāļāđāļāļāļĩāđāļĢāļēāđāļĄāļ āļāļĩāđāļĢāļĩāļĒāļĨ www.breastfeedingthai.com
- 46. âĒ āļāđāļēāļ§āđāļāđāļē āđāļāđāļ āļāđāļēāļ§āļŠāļ§āļĒ āļāđāļēāļ§āļāļĨāđāļāļ āļāđāļēāļ§āđāļŦāļāļĩāļĒāļ§ āđāļŠāđāļāļŦāļĄāļĩāđ āđāļŠāđāļāđāļĨāđāļ āđāļŠāđāļāđāļŦāļāđ āļāđāļ§āļĒāļāļąāļ āđāļāļĩāđāļĒāļĄāļāļĩāđ āļāļāļĄāļāļĩāļ āļāļļāļĒāļāđāļēāļĒ âĒ āļāđāļēāļ§āđāļāđāļ âĒ āļāđāļēāļ§āđāļāļ âĒ āđāļāđāļāļāļąāļāļ§āļĩāļ āđāļāđāļ āđāļŠāđāļāđāļāļāļ° âĒ āļāļąāđāļ§āđāļāļĩāļĒāļ§ āđāļāđāļ āļ§āļļāđāļāđāļŠāđāļ āđāļŠāđāļāđāļāļĩāđāļĒāļāđāļŪāđ āđāļāđāļēāļŠāđāļ§āļ āļĨāļđāļāļāļļāļ āļāļēāļŦāļĢāļīāđāļĄ âĒ āļāļąāđāļ§āđāļŦāļĨāļ·āļāļ āđāļāđāļ āļāļĄāļāļąāđāļ§āđāļŦāļĨāļ·āļāļ āļāđāļēāđāļāđāļēāļŦāļđāđ āđāļāđāļēāļŦāļđāđ āđāļāđāļēāđāļāļĩāđāļĒāļ§ āđāļāđāļēāļŪāļ§āļĒ āļāļĩāđāļāļīāđāļ§āļāđāļāļŠāļāļĢāļļāļāļĢāļŠāļāļēāļāļĒāļĩāđāļŦāđāļ āđāļāļĢāļēāļ°āļāļēāļāļĒāļĩāđāļŦāđāļāļāļ°āļĄāļĩāđāļāđāļāļŠāļēāļĨāļĩāļāļŠāļĄāļāļĒāļđāđ āļāđāļāļ āļāđāļēāļāļāļĨāļēāļāđāļŦāđāļĨāļ°āđāļāļĩāļĒāļāļāđāļ§āļĒāļāđāļ° âĒ āđāļāđāļāļĄāļąāļāļŠāļēāļāļ°āļŦāļĨāļąāļ āđāļāđāļ āļāļąāļāļāļīāļĄāļāļĢāļāļ āđāļāđāļāļĄāļąāļāļāļĩāđāđāļŠāđāļāļēāļŦāļēāļĢāļāļēāđāļŦāđāļŦāļāļ·āļāđāđāļāđāļ āđāļāđāļēāļŠāđāļ§āļ āļĢāļēāļāļŦāļāđāļē āļāļāļĄāļāļąāđāļ āļāļāļĄāļāļąāļāļāļāļ āļāļāļĄāļāļĨāđāļ§āļĒ āđāļĄāđāļ āļŠāļēāļāļđ âĒ āļāļąāđāļ§āđāļĄāļĨāđāļāđāļŦāđāļ āđāļāđāļ āđāļĄāļāļāļēāđāļāđāļĄāļĩāļĒ āļ§āļāļĨāļāļąāļ āļāļąāđāļ§āđāļāļ āļāļąāđāļ§āļāļēāļ§ āđāļĄāļĨāđāļāļāļāļāļāļēāļāļāļ°āļ§āļąāļ āđāļĄāļĨāđāļāļāļąāļāļāļāļ āđāļĄāļĨāđāļāđāļāļĨāđāļāļāđ āļāļąāđāļ§āļāļēāļāļāđāļē āļāļąāđāļ§āļāļīāļāļēāļāļīāđāļ āļĄāļ°āļĄāđāļ§āļāļŦāļīāļĄāļāļēāļāļāđ âĒ āļāļ·āđāļāđ āđāļāđāļ āļĄāļąāļāļāļĢāļąāđāļ āđāļŦāđāļ§ āđāļāļ·āļāļ āđāļŠāđāļāļāļļāļ āļĄāļąāļāđāļāļĻ āđāļāļ°āļāđāļ§āļĒ āļĨāļđāļāđāļāļ·āļāļĒ āļĨāļđāļāļāļąāļ§ āļāļē www.breastfeedingthai.com āļāļēāļŦāļēāļĢāļāļĩāđāļāļēāļāđāļāđ
- 48. Ketotifen is an orally active tricyclic benzocyclo-heptathiophene Derivative and thus may be a useful medication in the treatment and prevention of allergic responses. Ketotifen is a potent H1 receptor antagonist which has properties of mast cell stabilization and anti-inflammatory capabilities. Ketotifen also has other anti-inflammatory properties, which include reduced eosinophilic chemotaxis in eosinophilia and diminished production of eotaxin and expression of CD29 in epithelial cells.
Hinweis der Redaktion
- WDEIA one to four hours after wheat intake , but maybe delay or soon after exercise
- Semolina Spelt flour
- Increased gastrointestinal permeability , blood flow redistribution and increased osmolarity triggered by physical effort after exposure to a sensitizing food allegen
- Albumins and globulins, predominantly present in the aleurone layer and the germ, are mainly metabolic proteins. Gliadins and glutenins are storage proteins located in the starchy endosperm as a supply of nitrogen and amino acids for the seedling
- Gliadins are mainly monomeric proteins (molecular weights: 30 000â50 000) and glutenins are polymeric proteins linked by interchain disulphide bonds (molecular weights: 600 000 to more than 10 million). The chemical reduction of disulphide bonds results in glutenin subunits (molecular weights: 30 000 to 80 000). Based on similar amino acid sequences and molecular weights, gluten proteins can be classified into the following protein types [30]: a/b-, c-, x1,2-, and x5-gliadins, low-molecular-weight (LMW-GS), and high-molecular-weight glutenin subunits (HMW-GS). a/b-Gliadins, c-gliadins, and LMW-GS belong to the major and x5-gliadins, x1,2-gliadins, and HMW-GS to the minor components
- Synthetic overlapping dodecapeptides spanning the complete sequences (Pepscan) were used to identify the major immunogenic epitopes from a/b-gliadin, c-gliadin, x1,2-gliadin, and x5-gliadin [50]. All epitopes were localized in the glutamine- and proline-rich repetitive domains of the proteins. Cross-reactivity of allergens from barley, rye, and oats was studied, and among 23 patients with WDEIA, 21 showed IgE-binding to c-75k-secalin, 19 to c-40k-secalin, and 21 to c3- hordein; oat proteins did not cross-react
- strenuous exercise such as jogging, dancing, or cycling triggered anaphylaxis after food ingestion, but milder exercise, for example walking or gardening, may be sufficient
- Adaptive and innate immune responses to gluten in the gut. Ingested gluten is digested by gastrointestinal proteases in the small intestine to innocuous peptides or proteolytically resistant, glutamine (Q)-containing immunotoxic gluten peptides. Immunogenic gluten peptides access the lamina propria by unknown mechanisms. Their Q residues are deamidated to glutamic acid (E) by TG2, internalized by antigen-presenting cells (APC), and presented via HLA DQ2 (or DQ8) molecules on the surface of APC to gluten-specific, DQ2- and DQ8-restricted CD4+ T cells in the lamina propria. The subsequent activation and clonal expansion of the T cells results in a cell-mediated Th1 response that initiates destruction of the epithelial layer and villous flattening as well as a humoral response that stimulates gluten-specific and TG2-specific B cells to produce gluten- and TG2-specific antibodies. This renders the epithelium more permeable, facilitating increased access of immunogenic gluten peptides and propagation of disease. [Adapted from Bethune and Khosla (44).]
- Wheat (e.g., spelt) and other cereal grains (e.g., rye, barley) belong to the Poaceae family and share a number of homologous proteins among themselves and with grass pollen.93 Cereal grains are frequently implicated in foodÂallergic reactions in children with atopic dermatitis. On the basis of their solubility, wheat proteins can be classifed as water/saltÂsoluble albumins and globulins and water/saltÂinsoluble gliadins and glutenins.94 Among the major allergens identifed in the water/saltÂsoluble fraction of wheat ïŽour are the cereal ÎąÂamylase inhibitors (AAIs) and ÎąÂamylase/trypsin inhibitors (AATIs), which are capable of sensitizing by oral and inhaled routes (important allergens in bakerâs asthma and rhinitis). The globulin and glutenin fractions are the major allergenic fractions in IgEÂmediated reactions, as are gliadins in celiac disease and in foodÂassociated, exerciseÂinduced anaphylaxis (ÏÂ5 gliadin, Tri a 19).95,96 Lipid transfer proteins have been identifed as allergens in cases of reactions to beers brewed from barley and wheat. In a study of pediatric patients, 70 of 225 children were found to have at least one positive prick skin test to wheat, rye, oat, barley, rice, or corn: 28 of 70 to one grain, 16 of 70 to two grains, 12 of 70 to three grains, 6 of 70 to four grains, 6 of 70 to fve grains, and 2 of 70 to six grains.97 However, only 15 patients had at least one positive DBPCFC to a cereal grain; two children reacted to asthma. Gly m 1 (i.e., Gly m Bd30K/P34 or P34) is a soybean vacuolar protein that belongs to the group of nonspecifc lipid transfer proteins. Gly m 1 shares high sequence similarity to thiol proteinases of the papain family, which includes the major allergen in dust mites, Der p 1. Gly m 3 and Gly m 4 are related to birch pollen. With an amino acid sequence identity of 73%, Gly m 3 is highly homologous with the proflin Bet v 2. The IgEÂbinding epitopes of Gly m 3 are highly conformational, and fragments of Gly m 3 fail to bind IgE. Gly m 4, also called SAM 22 (starvationÂassociated message 22), is a PR protein with a 50% homology with Bet v 1. Serum IgE from 85% of birch pollenâallergic patients react to Gly m 4.72 About 10% of Central European patients sensitized to birch pollen have concomitant soy allergy, mainly due to crossÂreactivity with Gly m 4.73 Gly m 5 (ÎēÂconglycinin, 7S) and Gly m 6 (glycinin, 11S) are the seedÂstorage proteins from the cupin family that were found to be major allergens in a cohort of 30 patients with DBPCFCconfrmed soy allergy, suggesting that these molecules are good diagnostic markers of componentÂresolved in vitro testing. Gly m 5 and Gly m 6 have been associated with anaphylactic reactions in Japanese children.74 The allergenic epitopes on the Gly m 6 acidic chain are homologous with IgEÂbinding epitopes on peanut Ara h 3. Similar to highly refned peanut oil, refned soy oil did not provoke allergic reactions to soy in eight patients after ingesting up to 8 mL of soy oil.75 Tree nut allergies affect about 0.6% of the American population.3 In a national registry of peanut and nut allergic individuals, walnuts provoked the most allergic reactions (34%), followed by cashews (20%), almonds (15%), pecan (9%), pistachio (7%), and by hazel nut, Brazil nut, pine nut, and macadamia nut (all <5%).76 Skin testing reveals extensive crossreactivity among tree nuts. Although individuals allergic to one nut can tolerate other nuts, too few patients have been systematically challenged to a variety of nuts to determine the extent of clinical crossÂreactivity. High immunologic and clinical crossÂreactivity has been found between cashew and pistachio and between walnut and pecan.77 Patients allergic to nuts do not necessarily need to avoid peanuts (a legume) and vice versa. However, about 30% of peanutÂallergic patients also reacted to at least one tree nut.78,79 Fish are a common cause of foodÂallergic reactions in adults and in children.80 Edible fsh are found predominantly in the bony fsh class (Osteichthyes), in which there are hundreds of species. The major allergen in cod, Gad c 1, is a parvalbumin that has been isolated from the myogen fraction of the white meat. A similar protein, Sal s 1, has been isolated from salmon. It is heat stable and resistant to proteolytic digestion, has a molecular mass of 12 kD and an isoelectric point of 4.75, and is composed of 113 amino acids.81 Specifc IgEÂbinding epitopes have been identifed in Sal s 1; two of them correlate with those previously described in Gad c 1. The threeÂdimensional structure of Gad c 1 is arranged in three domains, two of which bind calcium. Using SDSÂPAGE and immunoblot analyses, 10 common fsh species were shown to have a protein that is similar to Gad c 1 and up to 29 protein fractions. Eleven patients with histories of fsh allergy had multiple positive skin test results for various fsh; 7 of 11 reacted to only one fsh species in DBPCFCs, 1 reacted to two fsh, 2 reacted to three fsh, and 1 patient did not react to any fsh during blinded challenges. The relative content of parvalbumin may underlie differences in allergenic potential, which is highest in white fsh (e.g., 1320 SECTION G Systemic Disease CARBOHYDRATE ALLERGENS The carbohydrate moieties present on many foods can induce IgE responses.35 Because carbohydrate moieties share signifcant structural homologies beyond that of proteins, they are prone to extensive crossÂreactivity and are referred to as cross-reactive carbohydrate determinants. Approximately 15% to 30% of allergic patients generate specifc antiglycan IgE, but very few develop clinical allergy. Bromelain was identifed as the frst food antigen that contained an oligosaccharide with two structural features that had not been found in mammalian glycoproteins: core Îą1,3Âfucose and xylose. GalactoseÂÎąÂ1,3Âgalactose (ÎąÂgal) has been identifed as a cause of serious, even fatal, anaphylaxis.99 In contrast to previously described crossÂreactive carbohydrate determinants expressed in plants and insects, the oligosaccharide ÎąÂgal is abundantly expressed on cells and tissues of nonprimate mammals. This expression pattern makes ÎąÂgal potentially clinically relevant as a food allergen (e.g., beef, pork, lamb) or as an inhaled allergen (e.g., cat, dog).100 IgE antibodies to ÎąÂgal are associated with an unusual form of delayed anaphylaxis, which occurs 3 to 6 hours after ingestion of mammalian meat that carries ÎąÂgal. Patients with IgE to ÎąÂgal describe generalized urticaria or frank anaphylaxis starting 3 to 6 hours after eating beef, pork, or lamb and have a consistent pattern of skin testing (likelihood of positive results is increased by testing with freshly ground meat or with intradermal testing) and serum IgE antibody results. Most patients developed anaphylaxis to red meat in adulthood; some reported receiving multiple tick bites, suggesting that tick bites, especially the lone star tick (Amblyomma americanum) may predispose to sensitization to ÎąÂgal. Food additives and colorings derived from natural sources that contain proteins may induce allergic reactions. They include colors derived from turmeric, paprika, seeds (e.g., annatto), and insects (e.g., carmine, cochineal). Chemical additives are not likely to cause IgEÂmediated food allergy, but some may have drug effects that cause adverse reactions, including allergyÂlike symptoms, or they may invoke immune responses. Tartrazine (yellow #5) is a synthetic color that has been extensively investigated because of concerns that it may trigger hives, allergic reactions, and asthma. However, wellconducted studies have not validated these concerns. Sulftes are added to foods as a preservative, an antibrowning agent, or a bleaching effect. In sensitive persons, sulftes may induce asthma. CROSS-REACTIVITY Structural homology among allergens underlies immunologic and clinical crossÂreactivity.101 More than 70% identity in primary sequence is considered necessary for clinical crossreactivity. However, the expression of clinical crossÂreactivity is modulated by additional factors, including: protein solubility and digestibility, concentration and affnity of the specifc IgE antibody, and the dose and route of allergen exposure. High rates of clinical crossÂreactivity are observed among milks from cows, goats, and sheep (>90%); melons (90%); crustacean shellfsh (75%); Rosaceae fruits such as apple, pear, peach (55%); and bony fsh (50%). Lower rates are observed among tree nuts (37%), grains (20%), cowâs milk and beef (10%), and peanuts and other legumes (5%). The rates of pollenÂfruit crossreactivity are about 50% for birch pollen and Rosaceae fruits. two grains, and two reacted to three grains. SDSÂPAGE and immunoblot analyses with patient sera revealed 27 to 31 protein bands in the range of 7.8Â66.5 kDa for each of the six cereal grains studied. Nonspecifc binding to lectin fractions was seen with each grain, and extensive immunologic crossÂreactivity occurred among the cereals, as was seen with skinÂprick testing. Homologies to allergenic proteins in grass pollens account for a large number of clinically irrelevant positive skin tests to wheat and other cereal grains. Wheat (e.g., spelt) and other cereal grains (e.g., rye, barley) belong to the Poaceae family and share a number of homologous proteins among themselves and with grass pollen.93 Cereal grains are frequently implicated in foodÂallergic reactions in children with atopic dermatitis. On the basis of their solubility, wheat proteins can be classifed as water/saltÂsoluble albumins and globulins and water/saltÂinsoluble gliadins and glutenins.94 Among the major allergens identifed in the water/saltÂsoluble fraction of wheat ïŽour are the cereal ÎąÂamylase inhibitors (AAIs) and ÎąÂamylase/trypsin inhibitors (AATIs), which are capable of sensitizing by oral and inhaled routes (important allergens in bakerâs asthma and rhinitis). The globulin and glutenin fractions are the major allergenic fractions in IgEÂmediated reactions, as are gliadins in celiac disease and in foodÂassociated, exerciseÂinduced anaphylaxis (ÏÂ5 gliadin, Tri a 19).95,96 Lipid transfer proteins have been identifed as allergens in cases of reactions to beers brewed from barley and wheat. In a study of pediatric patients, 70 of 225 children were found to have at least one positive prick skin test to wheat, rye, oat, barley, rice, or corn: 28 of 70 to one grain, 16 of 70 to two grains, 12 of 70 to three grains, 6 of 70 to four grains, 6 of 70 to fve grains, and 2 of 70 to six grains.97 However, only 15 patients had at least one positive DBPCFC to a cereal grain; two children reacted to asthma. Gly m 1 (i.e., Gly m Bd30K/P34 or P34) is a soybean vacuolar protein that belongs to the group of nonspecifc lipid transfer proteins. Gly m 1 shares high sequence similarity to thiol proteinases of the papain family, which includes the major allergen in dust mites, Der p 1. Gly m 3 and Gly m 4 are related to birch pollen. With an amino acid sequence identity of 73%, Gly m 3 is highly homologous with the proflin Bet v 2. The IgEÂbinding epitopes of Gly m 3 are highly conformational, and fragments of Gly m 3 fail to bind IgE. Gly m 4, also called SAM 22 (starvationÂassociated message 22), is a PR protein with a 50% homology with Bet v 1. Serum IgE from 85% of birch pollenâallergic patients react to Gly m 4.72 About 10% of Central European patients sensitized to birch pollen have concomitant soy allergy, mainly due to crossÂreactivity with Gly m 4.73 Gly m 5 (ÎēÂconglycinin, 7S) and Gly m 6 (glycinin, 11S) are the seedÂstorage proteins from the cupin family that were found to be major allergens in a cohort of 30 patients with DBPCFCconfrmed soy allergy, suggesting that these molecules are good diagnostic markers of componentÂresolved in vitro testing. Gly m 5 and Gly m 6 have been associated with anaphylactic reactions in Japanese children.74 The allergenic epitopes on the Gly m 6 acidic chain are homologous with IgEÂbinding epitopes on peanut Ara h 3. Similar to highly refned peanut oil, refned soy oil did not provoke allergic reactions to soy in eight patients after ingesting up to 8 mL of soy oil.75 Tree nut allergies affect about 0.6% of the American population.3 In a national registry of peanut and nut allergic individuals, walnuts provoked the most allergic reactions (34%), followed by cashews (20%), almonds (15%), pecan (9%), pistachio (7%), and by hazel nut, Brazil nut, pine nut, and macadamia nut (all <5%).76 Skin testing reveals extensive crossreactivity among tree nuts. Although individuals allergic to one nut can tolerate other nuts, too few patients have been systematically challenged to a variety of nuts to determine the extent of clinical crossÂreactivity. High immunologic and clinical crossÂreactivity has been found between cashew and pistachio and between walnut and pecan.77 Patients allergic to nuts do not necessarily need to avoid peanuts (a legume) and vice versa. However, about 30% of peanutÂallergic patients also reacted to at least one tree nut.78,79 Fish are a common cause of foodÂallergic reactions in adults and in children.80 Edible fsh are found predominantly in the bony fsh class (Osteichthyes), in which there are hundreds of species. The major allergen in cod, Gad c 1, is a parvalbumin that has been isolated from the myogen fraction of the white meat. A similar protein, Sal s 1, has been isolated from salmon. It is heat stable and resistant to proteolytic digestion, has a molecular mass of 12 kD and an isoelectric point of 4.75, and is composed of 113 amino acids.81 Specifc IgEÂbinding epitopes have been identifed in Sal s 1; two of them correlate with those previously described in Gad c 1. The threeÂdimensional structure of Gad c 1 is arranged in three domains, two of which bind calcium. Using SDSÂPAGE and immunoblot analyses, 10 common fsh species were shown to have a protein that is similar to Gad c 1 and up to 29 protein fractions. Eleven patients with histories of fsh allergy had multiple positive skin test results for various fsh; 7 of 11 reacted to only one fsh species in DBPCFCs, 1 reacted to two fsh, 2 reacted to three fsh, and 1 patient did not react to any fsh during blinded challenges. The relative content of parvalbumin may underlie differences in allergenic potential, which is highest in white fsh (e.g., 1320 SECTION G Systemic Disease CARBOHYDRATE ALLERGENS The carbohydrate moieties present on many foods can induce IgE responses.35 Because carbohydrate moieties share signifcant structural homologies beyond that of proteins, they are prone to extensive crossÂreactivity and are referred to as cross-reactive carbohydrate determinants. Approximately 15% to 30% of allergic patients generate specifc antiglycan IgE, but very few develop clinical allergy. Bromelain was identifed as the frst food antigen that contained an oligosaccharide with two structural features that had not been found in mammalian glycoproteins: core Îą1,3Âfucose and xylose. GalactoseÂÎąÂ1,3Âgalactose (ÎąÂgal) has been identifed as a cause of serious, even fatal, anaphylaxis.99 In contrast to previously described crossÂreactive carbohydrate determinants expressed in plants and insects, the oligosaccharide ÎąÂgal is abundantly expressed on cells and tissues of nonprimate mammals. This expression pattern makes ÎąÂgal potentially clinically relevant as a food allergen (e.g., beef, pork, lamb) or as an inhaled allergen (e.g., cat, dog).100 IgE antibodies to ÎąÂgal are associated with an unusual form of delayed anaphylaxis, which occurs 3 to 6 hours after ingestion of mammalian meat that carries ÎąÂgal. Patients with IgE to ÎąÂgal describe generalized urticaria or frank anaphylaxis starting 3 to 6 hours after eating beef, pork, or lamb and have a consistent pattern of skin testing (likelihood of positive results is increased by testing with freshly ground meat or with intradermal testing) and serum IgE antibody results. Most patients developed anaphylaxis to red meat in adulthood; some reported receiving multiple tick bites, suggesting that tick bites, especially the lone star tick (Amblyomma americanum) may predispose to sensitization to ÎąÂgal. Food additives and colorings derived from natural sources that contain proteins may induce allergic reactions. They include colors derived from turmeric, paprika, seeds (e.g., annatto), and insects (e.g., carmine, cochineal). Chemical additives are not likely to cause IgEÂmediated food allergy, but some may have drug effects that cause adverse reactions, including allergyÂlike symptoms, or they may invoke immune responses. Tartrazine (yellow #5) is a synthetic color that has been extensively investigated because of concerns that it may trigger hives, allergic reactions, and asthma. However, wellconducted studies have not validated these concerns. Sulftes are added to foods as a preservative, an antibrowning agent, or a bleaching effect. In sensitive persons, sulftes may induce asthma. CROSS-REACTIVITY Structural homology among allergens underlies immunologic and clinical crossÂreactivity.101 More than 70% identity in primary sequence is considered necessary for clinical crossreactivity. However, the expression of clinical crossÂreactivity is modulated by additional factors, including: protein solubility and digestibility, concentration and affnity of the specifc IgE antibody, and the dose and route of allergen exposure. High rates of clinical crossÂreactivity are observed among milks from cows, goats, and sheep (>90%); melons (90%); crustacean shellfsh (75%); Rosaceae fruits such as apple, pear, peach (55%); and bony fsh (50%). Lower rates are observed among tree nuts (37%), grains (20%), cowâs milk and beef (10%), and peanuts and other legumes (5%). The rates of pollenÂfruit crossreactivity are about 50% for birch pollen and Rosaceae fruits. two grains, and two reacted to three grains. SDSÂPAGE and immunoblot analyses with patient sera revealed 27 to 31 protein bands in the range of 7.8Â66.5 kDa for each of the six cereal grains studied. Nonspecifc binding to lectin fractions was seen with each grain, and extensive immunologic crossÂreactivity occurred among the cereals, as was seen with skinÂprick testing. Homologies to allergenic proteins in grass pollens account for a large number of clinically irrelevant positive skin tests to wheat and other cereal grains.
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