In accordance, recent bioinformatics supported guidelinesfor assessment of genetically modified crops suggest asequence identity of 35% as cut-off for potential crossreactivityThe pollen-specific IgE generated by this mechanism then binds to the surface of mast cells and basophils throughout the body, including those in the oropharyngeal mucosa. Upon oral contact with a related food, these IgE molecules recognize homologous proteins in the food, triggering localized release of inflammatory mediators and the symptoms of OAS. In most cases, the allergens are subsequently destroyed in the stomach, limiting any further reaction.
Conformational B cell epitopes in PFAS and OAS are sensitive to heat, acid, and digestive enzymes reaction usually limited to oropharynx.
Bet v1 specificIgE locate on mast cell can bind these food allergen upon ingestion, causing mediator release and oral syndrome
Beta 1,3 glucanases = catalyze the hydrolytic clevage of 1,3 beta-D-glucosidic
LTP : ทำหน้าที่ transfer phospholipid from liposome to mitochondria
In thiscontext, IgE antibodies directed against carbohydratesoccur in 25% of celery-allergic patients and it has beendemonstrated that N-glycans containing a1,3-fucose andb1,2-xylose (58) form the key IgE-binding epitopes ofcelery proteins with apparent MWs above 40 kDa
*Lacking evidence, these allergens are possible candidates to be involved in the pollen-food syndrome as listed in the table.LTPs, lipid transfer proteins; CCDs, cross-reactive carbohydrate determinants; high MW allergens, high-molecular weight allergens.Allergens not yet identified.Artemisia vulgaris, mugwort; Ambrosia artemisiifolia, ragweed; Chenopodium album, goosefoot; Plantagolanceolata, plantain.
Castor bean (Ricinuscommunis) : seed for costor oil Castor bean, mercury, and latex belong to the same botanical family of Euphorbiaceae and share common allergens; although no associations between castor bean andmercury with certain kinds of food have been observed, cross-reactions with foods involved in the latex-fruit syndrome cannot be ruled out.
Exceptions to this may be patients who have recently tolerated cooked forms of the food, whose systemic symptoms to raw food were not life-threatening, and who strongly desire to continue eating cooked forms
. However, there is some evidence that antihistamines can reduce the symptoms of OAS. In a randomized, placebo-controlled clinical trial, patients with birch allergy and hazelnut OAS who received a two week course of the H1-receptor antagonist, astemizole, had significantly reduced symptoms on oral challenge compared with placebo;
Oral allergy syndrome (OAS)• Oral allergy syndrome (OAS), referred to as pollen associated FA syndrome• localized IgE mediated allergy, usually to raw fruits or vegetables• OAS most commonly affects patients who are allergic to pollens Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel , J Allergy Clin Immunol 2010;126:S1-S58
OAS vs PFAS• Some pt. experience reaction to foods without pollinosis and symptom are not limited to oral cavity but may be range from oral and GI symptom to severe systemic reaction eg. Laryngeal edema, urticaria, bronchial asthma and food-induced anaphylaxis• Mari et al. defined OAS as complex of symptoms induced by exposure of the oral and pharyngeal mucosa to food allergens including symptoms of increasing severity1• OAS is not restricted to pollen-associated food allergies1• OAS due to a cross-reaction between pollen antigen and fruit or vegetable antigen has been called the more specific term “pollen-food allergy syndrome” (PFAS)2 1 Allergy 2006: 61: 461–476 2 Allergology International. 2009;58:485-491
Oral allergy syndrome (OAS)Clinical manifestration - usually restrict to oral cavity - After contact of fruit or vegetable rapid onset of itching of the lips, tongue, roof of the mouth, and throat, with or without swelling, and/or tingling of the lips, tongue, roof of the mouth, and throat - occassionally a sensation of pruritus in the ear and/or tightness in the throat - symptom are generally short-lived • Guidelines for the Diagnosis and Management of Food Allergy in the United States: Report of the NIAID-Sponsored Expert Panel , J Allergy Clin Immunol 2010;126:S1-S58 • Middleton’s Allergy principles & practice 7th edition, p 1150-51
Epidemiology• Estimated about 5% of general population in central Europe suffer from PFAS• PFAS affects up to 50-70% of adults suffering from pollen allergy, esp. to birch, ragweed, and mugwort pollens• Geographic and dietary influences complicate epidemiologic studies on pollinosis-associated food allergy, no exact data on the frequency of PFS is available • Middleton’s Allergy principles & practice 7th edition, p 1150-51 • Current Allergy and Asthma Report 2008,8:413-7
Pathogenesis• Cross reactivity occur when a specific antibody formed in response to one epitope react to another similar or identical epitope on anothor antigen• These pollen and foods are not botanically related but share highly conserved homologous protein called pan allergen (widely distributed throught the plant and animal kingdom)• IgE directed against common cross-reactive structures shared by pollen and plant-derived food Current Allergy and Asthma Report 2008,8:413-17
Pathogenesis• Sensitization to inhaled pollen proteins via the respiratory tract is believed to be the initial pathogenic event (Class 2 food allergy) Current Allergy and Asthma Report 2008,8:413-17
Cross-reactive Pan Allergens• Widely distributed throughout the plant kingdom and are involed in the extensive IgE cross- reactivity between antigen from unrelated plant species• Plant protein involved in PFAS - pathogenesis-related proteins (PRs) - lipid transfer protein (LTPs) - profilins -(cross-reactive carbohydrate determinant : CCD) Current Allergy and Asthma Report 2008,8:413-17
Pathogenesis-related protein (PRs)• 14 PRs familly• related to defense response to infection, wound healing, or environmental stress (drought, flood, freezing and ozone) in higher plant• Small molecular weight 5-70 kDa• Express different amount of PRP depending on environmental condition : ripeness, chemical, pesticides increase PRP expression (may enhance allergenicity) Current Allergy and Asthma Report 2008,8:413-17
Pathogenesis-related protein (PRs)• Bet.v1 is major allergenic protein in birch tree (Betula verrucosa) - PRP 10 - Most PFAS in birch pollen allergic pt. cause by protrein that have IgE cross-reactivity to Bet v1 and its food homologues : Rosacea fruit apple (Mal d 1), cherry(Pru av 1), apricort (Pru ar 1),pear (Pyr c 1), plum : Apiaceae vegetables celery(Api g 1), carrot(Dua c 1) - Mal d 1, major apple allergen, 63% homolog to Bet v1 Current Allergy and Asthma Report 2008,8:413-17
Pathogenesis-related protein (PRs) Fruit of the Rosaceae Vegetable of the Apiaceae Hazel nut Cor a1 These protein share a high degree of amino acid sequence similarity (28%-67%)to Bet v1 Middleton’s Allergy principles & practice 7th edition, p 1150-51
Pathogenesis-related protein (PRs)• PRs-2 - beta 1,3 glucanases - plant cell wall, these protein express during pollen germination and induced upon wounding, cold, ozone and UVB expose - Hev b 2 (latex allergen) sequence similar to beta 1,3 glucanases-like allergen in banana, potato, and tomato Current Allergy and Asthma Report 2008,8:413-17
Latex food syndrome Middleton’s Allergy principles & practice 7th edition, p 1150-51
Pathogenesis-related protein (PRs)• PRs-3 chitaneses class I, II, IV - only chitaneses class I associated with allergy - found in exoskeleton insect and cell wall of fungi - chitaneses class I have an N-terminal hevein domain that shared by latex prohevein (Hev b 6.02) - avocado, chestnut, and banana have sequence similar to chitaneses class I Current Allergy and Asthma Report 2008,8:413-17
Cross reactivity of latex-allergic pt. toavocado,chestnut, and banana Middleton’s Allergy principles & practice 7th edition, p 1150-51
Pathogenesis-related protein (PRs)• PRs-5 Thaumatin-like protein - antifungal in plantgive plants resist against freeze and drough (Minor allergen) (Major allergen) Current Allergy and Asthma Report 2008,8:413-17 Middleton’s Allergy principles & practice 7th edition, p 1150-51
PR-14 : LTPs (lipid transfer proeins)• 9 kDa polypeptides (plant antifungal and antibacterial)• Pan-allergen : widely distributed throughout the plant kingdom• Potent food allergen : thermostability and extreme resistance to pepsin digestion cause both PFAS and class 1 food anaphylaxis• LTPs retain allergenicity in process foods such as sterilized peach juice, cooked apple, beer, and ferment product such as wine• Sensitization to LTPs associated with higher rate of systemic reaction Current Allergy and Asthma Report 2008,8:413-17
• May responsible for fruit allergy in absence of pollen allergy• found in outer cell layer (peel > pulp) - Prunoideae family : peach (Pru p1 in peach skin and Pru p 3 in peach fruit), apricort (Pru ar 3), cherry (Pru av 3) - Rosaceae family : apple (Mal d 3), pear (Pyr c 3) - Gly m 1, a major allergen in soy bean• Apple allergic pt. without birch hypersensitivity frequence sensitized to apple LTPs (Mal d 3) (in southern Europe)• Mugwort pollen LTPs (Art v3) cross-react with peach LTPs(Pru p3) mugwort-peach association (esp. in Mediteranean area ) Current Allergy and Asthma Report 2008,8:413-17
Cherry Pru av 3Hazelnut Cor a 8Orange Cit s 3Strawberry Fra a 3Mugwort Art v 3 Middleton’s Allergy principles & practice 7th edition, p 1150-51
Profilin• 12–15 kDa actin-binding and cytoskeleton regulating protein• pan-allergen : prominent allergens in pollen of tree, grass, and weed• sensitization to profilin found 20% of pollen allergic pt.• First profilin identified was named Bet v2, IgE of birch pollen-food allergic individual cross-reacts with Bet v2 homologous protein from - apple ,pear, melon, carrot, celery, potato and mugwort Current Allergy and Asthma Report 2008,8:413-17
Mugwort Art v 4 Profilin Middleton’s Allergy principles & practice 7th edition, p 1150-51
High-molecular weight allergens andcross-reactive carbohydrate determinants (CCD)• 45–60 kDa• N-glycan stability to proteolysis & processing / thermostable• N-glycans containing 1,3-fucose & 1,2-xylose (glycoallergen) form the key IgE-binding epitope of celery protein (Api g 5) (cross-react with mugwort glycoprotein)• Celery-mugwort-spice syndrome in Mediterranean (rare Birch pollen): variable frequency of anaphylaxis Current Allergy and Asthma Report 2008,8:413-17
SYNDROMES ASSOCIATED WITHSYSTEMIC REACTIONS• Celery-birch-mugwort-spice syndrome - potentially severe form of celery allergy seen in patients who are sensitized to both birch and mugwort - Patients may react to the Apiaceae family (carrot, caraway, parsley, fennel, coriander, fenugreek, cumin, dill, and aniseed), as well as paprika, pepper, mango, garlic, leek, and onion Allergy 2006;61:461
• Can devide into at least 4 group 1. Api g 1,Bet v 1 homologous proteins demonstrated that IgE reactivity is based on primary sensitization to Bet v 1 in a central European population 2. Api g 4, profilin in celery display IgE cross-reactivity with birch Bet v 2 and mugwort Art v 4 profilins 3. Art v 60 kDa high MW allergens and/or CCDs (glycoallergens) recognized by IgEs cross –reacttivity from celery allergen Api g 5 4. Little known about cross reactions with Solanaceae or Piperaceae family Allergy 2006;61:461
• Mugwort profilin Art v4 celery mugwort spice syndrome• Bet v2 birch-celery association cross reactive of celery Api g 4
Ragweed melon banana association• Lack of molecular data on melon allergens possible cross- reactive allergen were identified in sera from OAS pt. - Profilin : allergenic conpound in other Cucurbitaceae fruit and vegetable eg. Zucchini, Cucurbita pepo - LTPs: 10% of melon allergic pt. display severe anaphylatic reaction (no melon LTPs has been idetified yet !!! ) - MW 15 to 60 kDa as allergens in melon, zucchini, cucumber, and watermelon seem to harbor complex asparagine-linked glycans comprising xyloxyl and fucosyl residues, which may act as CCDs Allergy 2006;61:461
• Latex-fruit syndrome - Approximately 30 % to 50 %of individuals who are allergic to natural rubber latex (NRL) show an associated hypersensitivity to some plant-derived foods, especially fresh fruits, such as avocado, banana, chestnut, kiwi, peach, tomato, white potato, and bell pepper - Allergens involved in the latex-fruit syndrome include hevein (Hev b 6.02), Hev b 7, and the panallergen profilin Hev b 8
Dignosis• No diagnostic criteria - A history of symptoms consistent with PFAS - Evidence of allergic sensitization to the plant food in question - Evidence of allergic sensitization to pollen - A known correlation between the plant food(s) in question and a pollen(s) to which the patient is sensitize• History - Has the patient experienced oropharyngeal symptoms, systemic symptoms, or both? - Are symptoms of pollen allergy present? - Has the patient reacted to other plant foods related to the one in question? - Are cooked forms of the food tolerated?
Diagnosis• Skin prick test - Prick to prick - Commercial extract• Specific IgE (immunoassays)• Oral food challenges :
DDx• Isolated food allergy• Local irritation of the mouth, tongue, or throat (spicy, tart, or gritty foods)• Contact urticaria (tomato sauce, citrus fruit, garlic, and berries local irritant contact urticaria of the lips and perioral skin esp. in children• Perioral dermatitis or oral contact dermatitis• Gastroesophageal reflux disease (GERD)• Eosinophilic esophagitis (EE)• Burning mouth syndrome
Treatment• Avoidance - specific raw fruits or vegetables or the nuts (roasted or raw) that have caused symptoms in the past - patients with mild symptoms limited to the oropharynx and wish to continue eating foods that cause symptom not restricting food intake - Patients with PFAS and systemic symptoms must avoid the raw form of the responsible food, should avoid cooked forms also
• If a patient wishes to continue eating cross-reactive foods - evaluate for allergy to the foods in question, If the test positive and patient wishes to continue eating foods, but have not eaten recentlyclinician-supervised oral food challenge to determine tolerance
• Antihistamines - not suggest premedicating with antihistamines in order to eat the fruit/vegetable masking symptoms by antihistamine may seduce pts to consume larger amounts of offending food & may lead to more severe symptom
• patients not experienced systemic reactions who should carry epinephrine autoinjectors ? - Allergy to peanut, tree nuts, or mustard has been objectively established - The patient experienced an oropharyngeal reaction to a cooked plant food - The patient had a positive SPT to a commercial extract for the culprit food - The patient reacted to a food that is associated with higher rates of systemic reaction in the geographical area (eg, a patient with allergy to apple living in Spain)
• Immunotherapy - 84% of birch pollen sensitive pt with birch pollen SCIT report significant reduction or disappearance of oral symptom to apple - 88% of these pt. experience marked reduction in SPT reactivity to apple Clinical and Experimental Allergy, 1998, Volume 28, pages 1368–1373 - 87% of birch allergic pt.with PFAS treat with SCIT could eat significant more apple or hazelnut without sign and symptom (small amount) Allergy 2004,59;1272-1276
• Immunotherapy - SLIT with birch pollen on PAFS to apple may enhance therapeutic efficacy in PFAS ??? no improvement in oral symptom to apple ingestion was note (in 9 pt.), improved nasal provocation score to birch pollen after SLIT J Allergy Clin Immunol 2007;119:937-43 Debate continue on therapeutic benefit of pollen immunotherapy for pollen food syndrome
Class 1 food allergy• Allergens eliciting class 1 food allergy (also termed complete food allergens) share special features, like resistance to gastric digestion, leading to the postulation that the sensitization process takes place in the gastrointestinal tract.• Major allergen are water soluble glycoprotein, molecular weight 10-70 kDa
Class 2 food allergy• class 2 food allergens : more sensitive to heat and digestive enzymes and cannot cause per-orally sensitizations, but instead provoke allergic reactions in already sensitized patients Incomplete sensitization or non sensitizing elicitors• According to their stability during the digestive process, they can cause symptoms ranging from mild oral reactions (typical for the birch-fruit syndrome) to anaphylatic shock (rare within the celery-mugwart-spice syndrome• Major allergen are plant-derived protein
Allergen in specific foodApple -Mal d 1, Bet v 1 homolog - highly unstable (heating, processing, and digestion) -Mal d 3, LTPs - highly resistant to heatingHazelnut -Cor a 1, Bet v1 homolog - Cor a 2,profilins - Cor a 8, LTPs - heat-stable systemic reactionPeanut Ara h 8, Bet v1 homologous partially disrupted by roated and complete destroyed by gastric enzymePeach - Profilin -central and northern Europe, oral - Pru p 3, LTPs symptom -Spanish pt. with anaphylaticSoy Gly m 4,homologous to Bet v 1 -Content depent on processing More process low reaction
Allergen in specific foodcarrot - Dau c 1,Bet v 1 homolog - cross react with celery, -profilin, a Bet v 6 cross- watermelon, apiaceous spices reactive allergen (fennel, coriander, caraway, - CCD aniseed), and birch and mugwort pollensKiwi fruit -Act c 1;actinidin (cysteine -OAS and severe systemic protease family) reactions, cross reactions with celery, rye, birch, mugwort, and timothy grass pollen, and latex - allergens in pollen-related kiwi -Act d 8,Bet v 1 homolog, allergy manifesting with less - Act d 9, profilin, severe symptoms.