Allergens in the Food Production Chain

Transcription

1 Allergens in the Food Production Chain Harry J. Wichers Agrotechnology and Food Sciences Group Animal Sciences Group Allergy Consortium Wageningen

2 Overview Allergies: What are they, and what are they not Incidence and prevalence Societal and economic costs Allergens: the cause of the adverse reaction What can be done about it? Sequence of events leading to allergic symptoms Interference points that result from this Conclusions and prospects

3 Overview Allergies: What are they, and what are they not Incidence and prevalence Societal and economic costs Allergens: the cause of the adverse reaction What can be done about it? Sequence of events leading to allergic symptoms Interference points that result from this Conclusions and prospects

4 What is an allergy-and what is not? Allergy: adverse, immune-mediated, reactions to otherwise harmless proteins Clinical symptoms in patients at allergen exposition: skin: atopic dermatitis: 10-12% gut: food allergy: 20% nose: rhinitis, hay fever: 10-20% lungs: asthma: %

5 What is an allergy-and what is not? Adverse reaction to food Non-toxic Toxic: Salmonella, etc. Intolerance: lactase-deficiency, strawberry, additives Allergic IgE-mediated Food allergy Direct effect on T-cell Coeliac disease

6 What is an allergy-and what is not? Sensitisation Elicitation APC Th0 cell IgE mast cell Th2 response histamine

7 What is an allergy-and what is not? An allergy is an adverse reaction to food, in which the immune system is involved

8 What is an allergy-and what is not?

9 Incidence and prevalence allergy = heritability x environment Genetic predisposition chance of allergy (%) no allergic parent or sibling one allergic parent one allergic parent+one allergic sibling both parents same allergy Nan N IM et al 1993, Dept. Immunol., EUR

10 Incidence and prevalence Factors that may cause allergy Smoking Pets Viral respiratory infections Bottle feeding Mites Month of birth allergy = heritability x environment food: faster market introductions less severe processing more resistant crops complex food products

11 The most important food allergies peanut /tree nuts 30% fish + shellfish egg 3% 8% cow's milk 10% 29% wheat 20% soya

12 Incidence and prevalence Increase of allergies in Europe allergic sensibilisation: 19 % (1991) 27 % (1995) asthma: 4 % (1973) 9 % (1988) eczema: 5 % (1973) 16 % (1988) Hay fever Source: UCB Allergy White paper, 1997

13 Incidence and prevalence Children: 6-8% Milk, egg, (pea)nut Adults: 1-2%; 4% Pitfalls in diagnosis Self-diagnosis Not-verified diagnosis Effects of protocols Geographical effects!

14 Incidence and prevalence Geographical distribution Sensitisation to apple allergens in NL, A, I and E median (U/ml) NL A I E 0 nmal d 1 rmal d 2 nmal d 3 rmal d 4 From: Suzanne Bolhaar, PhD-thesis, September 2004 Utrecht

15 Cross-reactivity Sicherer, JACI 108: 885 (2001)

16 Incidence and prevalence Biogenic factors infections, allergens Environment Anthropogenic factors stress, food Allergy is (more and more) an environmental disease Biology of effector organs immune system Individual Atopy family history Allergy develops at the interface between host and environment

17 Socio economic costs of allergic diseases Direct costs Hospital care Inpatient care Emergency services Outpatient services Physician services Laboratory diagnostic services Medications Indirect costs School days lost Work days lost Caregiver costs Allergen avoidance costs Early mortality loss Source: UCB European Allergy White Paper 10.4 billion + + EU 15, price level 1997 Pricelevel 2006 and EU-25: > 50 billion!! 18.9 billion 29.3 billion +

18 Overview Allergies: What are they, and what are they not Incidence and prevalence Societal and economic costs Allergens: the cause of the adverse reaction What can be done about it? Sequence of events leading to allergic symptoms Interference points that result from this Conclusions and prospects

19 Allergens: the cause of the adverse reaction Structural basis of allergenicity allergens epitopes allergens usually proteins epitopes active elements on the allergens linear epitope food allergens conformational epitope respiratory allergens

20 Allergens: the cause of the adverse reaction At the allergen level: Allergens abundantly present high/low exposure, medium affinity Relatively processing resistant (high C-C content) Relatively digestion resistant Together with: Vulnerability (e.g. immature gut) Genetic predisposition Environmental predisposition

21 Allergens: the cause of the adverse reaction Cupins Classification using Pfam database: Plants: Pfam 7.3, contains 3849 families; only 20 fam s contain allergens; 69% of allergens in 4 fam s: Cupins, LTP/2S-albumins, PR-10, profilins Prolamin Superfamily 2S albumins Brazil nut castor bean mustard sunflower α amylase/trypsin inhibitors rice wheat LTP (PR14) Peach sunflower Pollen related Bet v 1 (PR10) 7S globulins soya bean peanut 11S globulins soya bean peanut Thiol proteinases kiwi fruit soya bean papaya PR proteins β glucanase (PR2) chitinases(pr 3 and 4) thaumatin related (PRS) fruits vegetables Profilins fruit vegetables nuts Others Soya bean KI peanut lectin cereal peroxidases Animal: Pfam 21.0, contains 8957 fam s; majority of allergens in 3 fam s: Tropomyosins, EF-hand parvalbumins, caseins From: Mills et al. JACI 115: 163 (2005) Jenkins et al. JACI e-pub, 2007

22 Allergens: the cause of the adverse reaction PR-10 proteins: ca. 16 kda Steroid transport RN-ase Profilins: ca. 14 kda Sequestering actin monomers LTP s: ca. 9 kda Cutin formation 2S-albumins: ca kda Storage protein Cupins: ca kda; oligomers 7S-11S Storage proteins

23 Allergens: the cause of the adverse reaction Tropomyosin: ca. 37 kda Muscle protein (paramyosin) Parvalbumin: ca. 12 kda Transport protein E-F hand (collagen)

24 Allergens in cow s milk Casein (majority of protein) α, β, κ and γ (Bos d8) Whey-proteins α-lactalbumin β-lactoglobulin (Bos d4 and d5) Allergy Often and mostly with children Usually outgrowth after 1-2 jaar Prevalence: 5% 50% in VA + children

25 Allergens in cow s milk a

26 Overview Allergies: What are they, and what are they not Incidence and prevalence Societal and economic costs Allergens: the cause of the adverse reaction What can be done about it? Sequence of events leading to allergic symptoms Interference points that result from this Conclusions and prospects

27 What can be done about it Sensitisation Elicitation APC Th0-cell IgE mast cell Th2-response histamine Allergen avoidance

28 What can be done about it

29 What can be done about it Several allergens in each product Mal d 1-4 Mal d 1 labile Mal d 3 stable Ara h 1-9 Only Ara h 8 labile (Physical) processing sometimes successful. Success also depends on patients characteristics

30 What can be done about it Thresholds and severity of symptoms incidence none high symptoms severe allergen contents low

31 What can be done about it Thresholds and severity of symptoms incidence consumption none high symptoms severe allergen contents low Chocolate-spread-with-(no!)-hazelnut-case (NL) (Houben, Brussels, ): - Hazelnut protein mg/g - Trigger level < 1 mg (DBPCFC) - Consumption level 19±12 g/meal (max 60g) Risks for some products!

32 What can be done about it

33 What can be done about it

34 What can be done about it

35 What can be done about it

36 What can be done about it Zero-risk can not be achieved What is a societally acceptable risk? End-product control can not be realised in practice HACCP, labelling

37 What can be done about it Critical points: common sense! Suppliers, in-house production Separate raw materials Separate products Smart stocking: least allergenic items e.g. higher than allergenic items Planning of production process Hygiene in production facilities Detection

38 What can be done about it Proper labelling Avoid cross-contamination: HACCP Hidden allergens Courtesy Clare Mills, IFR-Norwich

39 What can be done about it Buckwheat Japan & South Korea Egg Milk Peanut Cereals containing gluten Tree nuts Crustaceans Fish Soybean Sesame seed Sulphites Celery Mustard Mollusks Lupin USA FALCPA Canada Australia New Zealand European Union Labelling Directive 2003/89/EG Adapted from Van Hengel, Anal Bioanal Chem 389: 111, 2007

40 What can be done about it Sensitisation Elicitation APC Th0-cell IgE mast cell Th2-response histamine Immunomodulation

41 What can be done about it Allergens promote Th2-response: Down-regulate this response Fungal protein restores the balance Th1 Th2 Wang et al. JAFC 52: 2721 (2003)

42 What can be done about it Immunomodulation Technology

43 Overview Allergies: What are they, and what are they not Incidence and prevalence Societal and economic costs Allergens: the cause of the adverse reaction What can be done about it? Sequence of events leading to allergic symptoms Interference points that result from this Conclusions and prospects

44 Examples from practice

45 Conclusions and prospects Allergenicity of food is the resultant of: Individual predisposition Exposure Life style The total of allergenic proteins Food matrix and processing Zero-risk does not exist HACCP offers better perspective than end-product control Labelling legislation should be based on threshold dosage and exposure data Future for immunomodulation? Time will tell!