3/9/2017. History. Is it allergy? What component? Which allergen?

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1 History What component? Is it allergy? Which allergen? Dr Cathy van Rooyen AMPATH Pathology Component testing can improve allergy diagnosis and patient management by enabling clinicians to: predict allergen cross-reactivity predict severity of reactions assist in dietary advice (some allergic patients may tolerate heated or processed foods or even peeled fruit) reduce the need for food challenges predict the likelihood that a patient may outgrow a food allergy select patients for allergen immunotherapy Component resolved allergy testing should not be used as a screening test or a first-line test, but as a second-line test after initial screening tests are positive. Natural allergen sources may contain many different proteins (components), but only a few of them are allergenic. Some of these protein components are species specific, but some occur in multiple allergen sources (cross-reactive components). The allergen component names include their scientific acronym and number (e.g. Ara h 2 means the second allergen from Arachis hypogaea or peanut). Patients with pollen allergies are often sensitised to cross-reactive components that occur in pollens as well as foods of plant origin. Food-pollen syndrome Allergy to furry animals When immunotherapy is considered Bee Allergy Latex allergy Food Allergy This may or may not be clinically relevant. This can be predicted by knowledge of allergenicity of certain protein groups, e.g. CCD < profilin < PR-10 < LTP. These components are the cause of the oral allergy syndrome (OAS). Some of these proteins are heat labile (profilin, PR-10) and some heat stable (LTP) important to advise whether patient should try cooking food. Some proteins are localised to certain areas in fruits, e.g. PR-10 in pulp, LTP in peel - tolerance to peeled fruit Be aware of cross-reactivity between pollens and food of plant origin: soya, wheat and peanut! 1

2 CROSS-REACTIVE COMPONENTS FOOD POLLEN SYNDROME: Severity of reaction CCD Profilin PR-10 LTP Localisation N/A Throughout Pulp of fruit Peel of fruit Stability to heat and digestion N/A Labile Labile Stable SYMPTOMSOF FOOD-POLLEN SYNDROME: CCD Profilin PR-10 LTP Usually no clinical Symptoms OAS OAS Mild to severe Symptoms OAS Severe clinical symptoms or anaphylaxis Mild reactions Unstable proteins Severe reactions Stable proteins WHEAT COMPONENTS WHEAT Ω 5 Gliadin Αβᴕω Gliadins Alpha Amylase/TI Profilin PR-10 LTP CCD Tri-a 19 Tri-a aa_ti Tri a 14 Risk marker for systemic reactions. Wheat allergy persistence Wheat dependent excercise induced anaphylaxis Marker of severe reactions Marker of wheat allergy persistence Inhaled wheat flour Baker s asthma Wheat dependent exercise induced anaphylaxis. PEANUT Storage Proteins Profilin PR-10 LTP CCD Ara h 1 Ara h 2 Ara h 3 Ara h 6 Ara h 5 Ara h 8 Ara h9 CCD Stable to heat and digestion Risk of anaphylaxis Cross-reactive with other nuts and seeds SOY Storage Proteins Profilin PR-10 LTP CCD Gly m 5 Gly m 6 Gly m 4 Associated with severe reactions May have severe reactions MILK COMPONENTS MILK EGG WHITE Ovomucoid Gal d 1 Highly allergenic Severe and persistent allergy Ovalbumin Gal d 2 Conalbumin Gal d 3 Heat labile May tolerate well-cooked egg Lyzozyme Gal d 4 EGG YOLK Egg serum albumin Gal d 5 Occurs in egg yolk, chicken meat and feathers Casein Bos d 8 Most important allergen Severe and persistent allergy Cross-reacts between mammals (eg: goat s milk) α lactalbumin Bos d 4 Β lactoglobin Bos d 5 Main whey proteins Heat labile Patients react more severely to fresh milk. May tolerate boiled/ baked milk, long-life milk, hard cheese and yoghurt. Bovine serum albumin Bos d 6 Occurs in milk and beef/ red meat. Heat labile, may tolerate well cooked milk and dairy. Cross-reaction with other mammals Lactoferrin Bos d lactoferrin Heat labile. May be used as a preservative in beef and nasal sprays. 2

3 Galactose-alpha-1,3-galactose Alpha-gal Bos d 6 Sugar structure found on glycoproteins of non-primate mammals. Sensitisation to α-gal may be induced by tick bites. Severe allergic symptoms and with delayed-type anaphylaxis. Cross-reaction with other mammals. Bovineserum albumin Occurs in milk and beef/ red meat. Heat labile, may tolerate well cooked meat. Cross-reaction with other mammals. FISH Cod pavalbumin Cyp c 1 Carp parvalbumin Gad c 1 Broad cross-reactivity, marker for general fish sensitization. Parvalbumin content of different fish species may vary, e.g. lower levels in tuna. SHELLFISH Tropomyosin Pen a 1 muscle protein. Found in crustaceans, molluscs, insects and mites with clinical crossreactivity. Arginine Kinase Pen m 2 True shellfish sensitisation. Allergen component testing is available as: Individual ImmunoCap components. ISAC, a multiplex assay containing 112 different allergen components. Components predicting IT success IT not recommended Other pitfalls Grass Cat Dog Horse Mite Bee Grass group 1 Phl p 4 Phl p 7 Phl p 11 Grass group 1 in Bermuda grass can cross-react with maize pollen Fel d 1 Can f 1 Can f 2 Fel d 2 (Serum albumin) Fel d 4 Lipocalin cross-reacts with dog, horse, cow Can f 5 Can f 3 (Serum albumin) Can f 1, 2 are lipocalins can crossreact with other lipocalins Equ c 1 Der p 1 Der p 2 Equ c 3 (Serum albumin) Equ c 1 is a lipocalin that can crossreact with Fel d 4 (cat) Der p 10 (Tropomyosin) Blo t 5 positive Blomia tropicalis doesn t crossreact with other mites seperate IT required. Api m1 Api m 3 Api m 10 Bee and wasp crosssensitisation; ves v 1, v 5 CCD crossreactivity Who will benefit from ISAC testing? Patients with multiple allergies Patients with combined food and inhalant allergies Patients with suspected allergen cross-reactivity When to request individual ImmunoCap components? Clear history of sensitisationwhere specific cross-reactions are suspected. Where specific food allergies are being investigated Before immunotherapy Unfortunately the amount of component allergens available as single specific ImmunoCap tests is still limited. That the main allergen components indicating risk of severe allergic reactions and adding clinical value be tested when the source allergen test is positive: That cross-reactive pollen components be tested in patients with pollen allergy and combined sensitisation to peanut, soy and wheat: Egg white: ovomucoid IgE Milk: casein IgE Peanut: Ara h 2 IgE Codfish: parvalbumin IgE Wheat: omega-5-gliadin IgE CCD IgE LTP IgE PR-10 IgE Profilin IgE 3

4 9 year old boy Atopic history, childhood eczema, allergic rhinitis, mild asthma. History of CMA in childhood, but has subsequently outgrown this allergy and tolerates all dairy products. Mom suspects he is allergic to dust, grass, dogs and cats, but he has recently also developed new food allergies. Systemic symptoms: bronchospasm and angioedema within minutes after consuming seafood (fish and shellfish). Can tolerate tinned tuna. No other fish. Reacts with oral itching and swelling of his throat after eating tree nuts, peanuts, banana, avocado and melon. Mild oral reaction to whole wheat bread (white bread fine). No difference between peeled/unpeeled fruit. Cooking vegetables / fruits results in fewer symptoms. IMMUNOGLOBULINS Total IgE H ku/l FOOD ALLERGENS Food Mix IgE H ku/l BREAKDOWN Egg white IgE ku/l Codfish IgE H ku/l Milk IgE ku/l Wheat IgE H ku/l Soya IgE H ku/ Peanut IgE H ku/l ISAC BERMUDA GRASS Grass Group 1 Allergen H ISU TIMOTHY GRASS Grass Group 1 Allergen H ISU Grass Group 2 Allergen ISU Berberine Bridge Enzyme H ISU Grass Group 5 Allergen ISU Grass Group 6 Allergen ISU Ca Binding 2-EF-hand Protein ISU Ole e-related Protein ISU Profilin H ISU BIRCH Profilin H ISU Ca Binding 2-EF-hand Protein ISU ALDER MUGWORT Defensin ISU Lipid Transfer Protein (nsltp) H ISU GOOSEFOOT Che a 1 trypsin inhibitor ISU PLANTAIN ENGLISH Pla l ISU WALL PELITORY Lipid Transfer Protein (nsltp) ISU SALTWORT Pectin Methylesterase ISU ANNUAL MERCURY Profilin H ISU KIWI Cysteine Protease ISU Thaumatin-like Protein ISU Kiwellin ISU CELERY APPLE PEACH Lipid Transfer Protein (nsltp) H ISU CASHEW NUT Legumin-like Protein ISU PEANUT Storage Protein 7s Globulin ISU Storage Protein Conglutin ISU Storage Protein 11s Globulin ISU nara h ISU Lipid Transfer Protein (nsltp) H ISU BRAZIL NUT Storage Protein 2s Globulin ISU HAZEL NUT Lipid Transfer Protein (nsltp) H ISU Storage Protein 11s Globulin ISU WALNUT Storage protein, 2S albumin ISU Storage protein, 7S globulin ISU Lipid Transfer Protein (nsltp) H ISU SOY BEAN Storage Prot Beta-conglycinin ISU Storage Protein Glycinin ISU SESAME SEED Storage Protein 2s Albumin ISU WHEAT Omega-5 Gliadin ISU a-amylase/trypsin Inhibitor ISU nfage 2(16kD) ISU Lipid Transfer Protein (nsltp) H ISU 4

5 LATEX Rubber Elongation Factor ISU Small Rubber Particle Protein ISU Acidic Protein ISU Hevein ISU Profilin H ISU BROMELIN CCD/MUXF3 H ISU MILK Alpha-lactalbumin ISU Beta-lactoglobulin ISU Casein ISU Transferrin Milk ISU COW EGG Ovomucoid ISU Ovalbumin ISU Conalbumin ISU COD Parvalbumin H ISU SHRIMP Tropomyosin (Pen m 1) H ISU Pen m ISU Pen m ISU D.FARINAE (HOUSE DUST MITE) Cysteine Protease H ISU NPC2 Family H ISU D.PTERONYSSINUS (HOUSE DUST MITE) Cysteine Protease H ISU NPC2 Family H ISU Tropomyosin H ISU STORAGE MITE Blo t ISU Lep d ISU DOG Lipocalin (Can f 1) ISU Lipocalin (Can f 2) ISU Arginine esterase H ISU HORSE Lipocalin H ISU CAT Uteroglobin H ISU Serum Albumin H ISU Lipocalin H ISU MOUSE Lipocalin H ISU ALTERNARIA Acidic Glycoprotein ISU Enolase ISU ASPERGILLUS Mitogillin ISU Peroxysomal Protein ISU Mn Superoxide Dismutase ISU CLADOSPORIUM Mannitol Dehyrogenase ISU HONEY BEE Phospholipase A ISU Melittin ISU WASP Ves v ISU Pol d ISU COCKROACH Cockroach Group ISU Aspartic Protease Group ISU Glutathione S-transferase ISU Tropomyosin ISU INTERPRETATION ANISAKIS Serine Protease Inhibitor ISU Tropomyosin ISU Interpretation RANGE(ISU) INTERPRETATION <0.3 Undetectable Low Moderate High >15 High Inhalant allergy: grass pollen, house dust mite, cat, dog. IgE to cross-reactive pollen-derived components: profilin, LTP, CCD. Profilin levels highest and clinically profilin is most significant. LTP also seems to play a role (peanut, wholewheat) Fish: parvalbumin, all fish species. (Tuna lowest levels of parvalbumin expression) Shellfish: tropomyosin (cross-reacts with house dust mite) Cat: true allergy cross-sensitisation to horse, mouse, etc. Dog: true allergy, may react to male dogs only. 5

6 We can know who to challenge. CONCLUSION Component based testing has a major impact on allergy practice. We can provide practical dietary advice to patients with food allergies and prevent unnecessary avoidance. We can provide effective immunotherapy based on primary sensitising allergens. We can help patients with multiple and complex allergies. 6