Food Allergy & Intolerance

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1 Food Allergy & Intolerance Marcos Alcocer Food Waste Utilisation & Alternative Proteins Workshop 28/11/2017 Associate Professor School of Biosciences Sutton Bonington campus University of Nottingham,UK

2 You tube animation: mp4 or media centre With the end of our own vegetable gardens..in our industrialised world Quino Not everything is exactly under our control EFA

3

4 Classification

5 Classification Adverse Reactions to Food Non toxic toxic Immune mediated Non immune mediated Unknown Aversion (psychosomatic) Non IgE mediated Proctocolitis, Enterocolitis, Coeliac disease Eosinophilic esophagitis Enzymatic Intolerance to lactose, Alcohol, galactosemia IgE mediated Anaphylaxis, Oral allergy syndrome Exercise induced anaphylaxis Pharmacological Caffeine, acids,tyramine Alkaloids, Histamine, Monosodium glutamate, Salicylates, Benzoates Based on 2000, COT report and Skypala et al, food hypersensitivity.

6 Classification Adverse Reactions to Food Non toxic toxic Food hypersensitivity Immune mediated Non immune mediated Unknown Aversion (psychosomatic) Non IgE mediated Proctocolitis, Enterocolitis, Coeliac disease Eosinophilic esophagitis Enzymatic Intolerance to lactose, Alcohol, galactosemia IgE mediated Anaphylaxis, Oral allergy syndrome Exercise induced anaphylaxis Pharmacological caffeine, acids,tyramine Alkaloids, Histamine, Monosodium glutamate, Salicylates, benzoates Based on 2000, COT report and Skypala et al, food hypersensitivity.

7 Classification Adverse Reactions to Food Food allergy Non toxic Food hypersensitivity toxic Immune mediated Non immune mediated Unknown Aversion (psychosomatic) Non IgE mediated Proctocolitis, Enterocolitis, Coeliac disease Eosinophilic esophagitis Enzymatic Intolerance to lactose, Alcohol, galactosemia IgE mediated Anaphylaxis, Oral allergy syndrome Exercise induced anaphylaxis Pharmacological caffeine, acids,tyramine Alkaloids, Histamine, Monosodium glutamate, Salicylates, benzoates Based on 2000, COT report and Skypala et al, food hypersensitivity.

8 What is Food allergy? It is Immunity Gone Wrong

9 The Gut is Bombarded by Foreign Antigens No Response (Tolerance) Eradication Containment Disease Response Activation of mucosal mast cells Release of inflammatory mediators Transepithelial fluid loss Smooth muscle contraction Vomiting and diarrhoea (Immune Activation) Anaphylaxis mucosal barrier

10 The Gut sampling system Watch full Nature video in youtube:

11 An allergic (atopic) patient: Video

12 Symptoms: National Institute of Allergic diseases- Boyce et al, 2010, J Allergy Clin Immunol. symptoms of acute IgE responses (sneezing, coughing, vomiting, diarrhoea, itch) evolved as protection against helminthic, irritants, toxins venoms, hematophagus fluids and phytochemicals Palmer et al, Nature 2012,484: It is not known why food in particular provoke different constellations of symptoms in different individuals.

13 Is food allergy a problem?

14 If your source is newspapers only:

15 Urticaria

16 Eczema

17 Systemic Anaphylactic shock Courtesy Dr Jane Lucas

18 Systemic Anaphylactic shock A 10-Year-Old Child with Food-Induced Anaphylaxis. The endotracheal tube and angioedema of the lip are shown. Lack G. (2008) New England J Med. 359:

19 Incidence Atopic march Asthma Rhinitis Age (years) Eczema Food allergy 64 Redrawn from Durham SR & Church MK, Allergy 2 nd edition, 2001, Mosby

20 Could food allergy be fatal?

21 People.. children dead by Food early reports

22 Fatal cases Baby death nursery fined A nursery where an allergic child died after eating a milk product has been fined 60,000 and has been ordered to pay 19,000 costs. Jigsaw Day Nurseries Ltd was sentenced at Aylesbury Crown Court on Thursday. Thomas Egan, who was five months old, had been diagnosed with an allergy to all dairy products. A nurse at the Jigsaw Day Nursery in Browns Wood, Milton Keynes, fed Thomas a breakfast cereal, not realising it contained milk.

23 Food allergy fatalities UK Pumphrey, Clin Exp Allergy, 2000

24 Location Food allergy fatalities UK Pumphrey, Clin Exp Allergy, 2000

25 Problems with data acquisition Patterns of sensitisation Birch pollen Apple, pear Mald 1???? Apple, pear LTP

26 Diagnosis

27 Diagnosis algorithm (egg Allergy) (2008) New England J Med. 359:

28 Skin Prick Test Method such as Skin Prick Test (SPT) despite its severe limitations is still widely used.but

29 A4.514 A A7.753 A8.755 A9.757 E4.514 E E7.753 E8.755 E9.757 G4.514 G G7.753 G8.755 G9.757 M4.514 M M7.753 M8.755 M9.757 Complex analysis, Immune Profiling is now possible #21 Plant / Vegetable Fruits Herbs / Spices Seeds Meat Fish Shellfish Beans Nuts Dog Inhaled Allergens Others Cereals/roots Shellfish Seeds Plant / Vegetable Cereals/roots Dairy Eggs Others Drink / Sauce Antibodies Inhaled Allergens Enterobacteria Cat

30 Complex analysis, Immune Profiling is now possible Wulfert et al (2012) J Immunol Meth

31

32 Allergens

33 Key players in Allergy Basophil (or mast cell) Immunoglobulin E Allergens IgE Receptor Cross-linking degranulation Mediator release Histamine Leukotrienes cytokines

34 Few food products are implicated in anaphylactic reactions >90% Very few protein families are actually allergenic

35 Availability of sequences has revolutionised our understanding of the evolutionary biology of allergens Currently protein expression, Large databases, robotics.. Extracts-> Component Resolved Diagnostics Radauer & Breiteneder 2007, J allergy Clin Immunol

36 Legislation: Commission Directive 2007/68/EC (EFSA) EC Regulation 1169/2011 (Dec 2014) 1. Cereals containing gluten (i.e. wheat, rye, barley, oats, spelt, kamut or their hybridised strains) and products thereof,except: (a) wheat-based glucose syrups including dextrose; (b) wheat-based maltodextrins (c) glucose syrups based on barley; (d) cereals used for making distillates or ethyl alcohol of agricultural origin for spirit drinks and other alcoholic beverages. 2. Crustaceans and products thereof. 3. Eggs and products thereof. 4. Fish and products thereof, except: (a) fish gelatine used as carrier for vitamin or carotenoid preparations; (b) fish gelatine or Isinglass used as fining agent in beer and wine. 5. Peanuts and products thereof. 6. Soybeans and products thereof, except: (a) fully refined soybean oil and fat (b) natural mixed tocopherols (E306), natural D-alpha tocopherol, natural D-alpha tocopherol acetate, natural D-alpha tocopherol succinate from soybean sources; (c) vegetable oils derived phytosterols and phytosterol esters from soybean sources; (d) plant stanol ester produced from vegetable oil sterols from soybean sources

37 Legislation: Commission Directive 2007/68/EC (EFSA) EC Regulation 1169/2011 (Dec 2014) 7. Milk and products thereof (including lactose), except: (a) whey used for making distillates or ethyl alcohol of agricultural origin for spirit drinks and other alcoholic beverages; (b) lactitol. 8. Nuts, i.e. almonds (Amygdalus communis L.), hazelnuts (Corylus avellana), walnuts (Juglans regia), cashews (Anacardium occidentale), pecan nuts (Carya illinoiesis (Wangenh.) K. Koch), Brazil nuts (Bertholletia excelsa), pistachio nuts (Pistacia vera), macadamia nuts and Queensland nuts (Macadamia ternifolia), and products thereof, except: (a) nuts used for making distillates or ethyl alcohol of agricultural origin for spirit drinks and other alcoholic beverages. 9. Celery and products thereof. 10. Mustard and products thereof. 11. Sesame seeds and products thereof. 12. Sulphur dioxide and sulphites at concentrations of more than 10 mg/kg or 10 mg/litre expressed as SO Lupin and products thereof. 14. Molluscs and products thereof.

38 Change tactics: Be more selective on Your suppliers Quino

39 Help, guidance, links, Legislation

40 Help, guidance, links American Academy of Allergy Asthma and Immunology (AAAAI) Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S1-148.

41 Help, guidance, links American Academy of Allergy Asthma and Immunology (AAAAI) Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S European Academy of Allergy Clinical Immunology (EAACI) European Academy of AC, Immunology. Allergen standardization and skin tests. European Journal of Allergy and Clinical Immunology. 1993;48:48-82.

42 Help, guidance, links American Academy of Allergy Asthma and Immunology (AAAAI) Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S European Academy of Allergy Clinical Immunology (EAACI) European Academy of AC, Immunology. Allergen standardization and skin tests. European Journal of Allergy and Clinical Immunology. 1993;48: National Institute of Allergy and Infections Disease (USA) Chafen et al., Prevalence, natural history, diagnosis and treatment of Food Allergy, a systematic review of evidences, 2010, RAND Health Boyce et al., Guidelines for the diagnosis and management of foof allergy in the United States, J Allergy Clin Immunol 2010, 126(6):S5

43 Help, guidance, links American Academy of Allergy Asthma and Immunology (AAAAI) Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S European Academy of Allergy Clinical Immunology (EAACI) European Academy of AC, Immunology. Allergen standardization and skin tests. European Journal of Allergy and Clinical Immunology. 1993;48: National Institute of Allergy and Infections Disease (USA) Chafen et al., Prevalence, natural history, diagnosis and treatment of Food Allergy, a systematic review of evidences, 2010, RAND Health Boyce et al., Guidelines for the diagnosis and management of foof allergy in the United States, J Allergy Clin Immunol 2010, 126(6):S5 European Federation of Asthma and Allergy Association

44 Help, guidance, links American Academy of Allergy Asthma and Immunology (AAAAI) Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S European Academy of Allergy Clinical Immunology (EAACI) European Academy of AC, Immunology. Allergen standardization and skin tests. European Journal of Allergy and Clinical Immunology. 1993;48: National Institute of Allergy and Infections Disease (USA) Chafen et al., Prevalence, natural history, diagnosis and treatment of Food Allergy, a systematic review of evidences, 2010, RAND Health Boyce et al., Guidelines for the diagnosis and management of food allergy in the United States, J Allergy Clin Immunol 2010, 126(6):S5 European Federation of Asthma and Allergy Association (EFAAA/EAACI) American College of Allergy, Asthma and Immunology (ACAACI)

45 Help, guidance, links American Academy of Allergy Asthma and Immunology (AAAAI) Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S European Academy of Allergy Clinical Immunology (EAACI) European Academy of AC, Immunology. Allergen standardization and skin tests. European Journal of Allergy and Clinical Immunology. 1993;48: National Institute of Allergy and Infections Disease (USA) Chafen et al., Prevalence, natural history, diagnosis and treatment of Food Allergy, a systematic review of evidences, 2010, RAND Health Boyce et al., Guidelines for the diagnosis and management of food allergy in the United States, J Allergy Clin Immunol 2010, 126(6):S5 European Federation of Asthma and Allergy Association American College of Allergy, Asthma and Immunology (ACAACI) Anaphylaxis Campaign (UK)

46 Help, guidance, links American Academy of Allergy Asthma and Immunology (AAAAI) Bernstein IL, Li JT, Bernstein DI, Hamilton R, Spector SL, Tan R, et al. Allergy diagnostic testing: an updated practice parameter. Ann Allergy Asthma Immunol. 2008;100(3 Suppl 3):S European Academy of Allergy Clinical Immunology (EAACI) European Academy of AC, Immunology. Allergen standardization and skin tests. European Journal of Allergy and Clinical Immunology. 1993;48: National Institute of Allergy and Infections Disease (USA) Chafen et al., Prevalence, natural history, diagnosis and treatment of Food Allergy, a systematic review of evidences, 2010, RAND Health Boyce et al., Guidelines for the diagnosis and management of food allergy in the United States, J Allergy Clin Immunol 2010, 126(6):S5 European Federation of Asthma and Allergy Association American College of Allergy, Asthma and Immunology (ACAACI) Anaphylaxis Campaign (UK) Food Allergy and Anaphylaxis Anaphylaxis Network (USA)

47

48 Questions?

49 Adrenaline injections Adrenaline is the drug of choice in first line treatment of anaphylaxis because it works quickly to reverse the symptoms of an anaphylactic reaction. Adrenaline constricts blood vessels causing a rise in blood pressure, relaxes smooth muscle in the lungs to improve breathing, stimulates the heart beat and reduces swelling around face and lips. Slit immunotherapy:

50 Adrenaline injections

51 Oral allergy syndrome (1) OAS is elicited by a variety of plant proteins, especially pathogenesis-related proteins, cross-reacting with airborne allergens. Symptoms are provoked almost exclusively in the oropharynx and rarely involve other target organs. It is estimated that OAS affects up to 50% to 70% of adults suffering from pollen allergy, especially to birch, ragweed, and mugwort pollens. Ragweed allergic patients may experience OAS following contact with various fresh melons (e.g., watermelon, cantaloupe, honeydew) and bananas. Birch pollen allergic patients may develop symptoms following the ingestion of raw potatoes, carrots, celery, apples, pears, hazelnuts and kiwi.

52 Class 1 Food Allergens (1): Protein Fraction Protein (%) M.W. (kd) Nomenclature Cow's Milk Caseins α s1 -Casein Bos d 8 α s2 -Casein β-casein κ-casein Whey β-lactoglobulin Bos d 5 α-lactalbumin Bos d 4 Serum albumin Bos d 6 Sensitization to food allergens may occur in the gastrointestinal tract, considered "traditional" or class 1 food allergens... Chicken Egg White Ovalbumin Gal d 1 Ovomucoid Gal d 2 Ovotransferrin Gal d 3 Peanut Vicilin Ara h 1 Conglutin - 17/19 Ara h 2 Glycinin - 64 Ara h 3 Soybean Glycinin G1 acidic chain - 40 Profilin - 13 Gly m 3 Fish Parvalbumin Gad c 1 Shrimp Tropomyosin - 36 Pen a 1

53 Class 2 Food Allergens (Cross-reactive and Associated with Oral Allergy Syndrome) (1) Protein Nomenclature Protein Fraction Latex-Fruit Cross-reactivity Pathogen-related protein 2 group M.W. (kd) Latex Avocado Banana Chestnut Fig Kiwi Hev b 2 1,3 gluconase 34/36 Pathogen-related protein 3 group Latex Avocado Chestnut Hev b 6.02 Pers a 1 Pathogen-related protein 5 Apple Mal d 2 Chitinase Endochitinase Thaumatinhomologue 5 32 Cherry Pru av 2 Thaumatin 23.3 Birch Bet v 1 Homologues (pathogen-related proteins 10) Apple Mal d 1 Bet v 1 homologue Cherry Pru av 1 Bet v 1 homologue Apricot Pru ar 1 Bet v 1 homologue Pear Pyr c 1 Bet v 1 homologue 18 Carrot Dau c 1 Bet v 1 homologue Celery Api g 1 Bet v 1 homologue 16 Parsley pcpr 1 and 2 Bet v 1 homologue Hazelnut Cor a 1 Bet v 1 homologue or as a consequence of an allergic sensitization to inhalant allergens, considered class 2 food allergy Birch Bet v 2 Homologues (celery-mugwort-spice syndrome) Latex Hev b 8 Profilin 14 Celery Api g 4 Profilin Potato Profilin Cherry Pru av 4 Profilin 15 Pear Pyr c 4 Profilin 14 Peanut Ara h 5 Profilin 15 Soybean Gly m 3 Profilin 14

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