1. Food Allergies: Whats New in Clinical, Community, School and Food Service Applications Janice M. Joneja, Ph.D., RD 2006

2. 2 Food Allergy in the Past 5 Years Nearly 4% of North Americans have food allergies, many more than recorded in the past –Incidence of food allergy much higher in children (>8%) than adults ( 8%) than adults (<2%) Prevalence of peanut allergy doubled in American children younger than 5 years of age in the past 5 years

3. 3 Food Allergy in the Past 5 Years Incidence of food intolerances estimated to be up to 50% of the population, but accurate figures are not available because of the lack of appropriate tests –Incidence of food intolerances much higher in adults than in children Many food allergens have been characterized at the molecular level, leading to increased understanding of the causes of many allergic disorders

4. 4 Food Allergy & Food Intolerance Food Allergy A response of the immune system to an ingested food or food additive Is not dose-dependent Food Intolerance A generic term describing an abnormal physiological response to an ingested food or food additive which is not a result of a response of the immune system Is dose-dependent

5. 5 Management of Food Allergies and Intolerances Management of food sensitivities consists of: –Accurate identification of the food causing the problem –Educating clients on how to avoid relevant allergens and intolerance triggers in foods –Formulating appropriate diets to avoid the culprit foods and replacing them with foods of equivalent nutritional value –Educating parents in measures to: avoid sensitization of their at-risk babies avoid sensitization of their at-risk babies induce tolerance of foods induce tolerance of foods

6. 6 The Allergic Diathesis. Food Allergy Atopic dermatitis (Eczema) Allergic rhinoconjunctivitis (hay fever) Asthma (cough; wheeze) Gastrointestinal symptoms Sleep deprivation Anaphylaxis Mental fogginess Irritability Fatigue In infants: failure to thrive

7. 7 Allergy is a Response of the Immune System Our immune systems are designed to protect the body from invasion by foreign materials T cell lymphocytes detect foreign proteins (antigens) in any form T cells then trigger a series of immunological reactions, mediated by cytokines

8. 8 Antigen Recognition The first stage of an immune response is recognition of a foreign antigen (protein or glycoprotein) The first stage of an immune response is recognition of a foreign antigen (protein or glycoprotein) T cell lymphocytes are the controllers of the immune response T cell lymphocytes are the controllers of the immune response T helper cells (CD4+ subclass) (Th) identify the foreign protein as a potential threat T helper cells (CD4+ subclass) (Th) identify the foreign protein as a potential threat

9. 9 Education of the Immune System All foods contain proteins – derived from plants and animals – all of which are foreign to the human body In order for food to be absorbed, metabolized, and utilized by the body, the immune system needs to be educated that the foreign material is safe This involves a complex series of immunological reactions

10. 10 Immune System of the Digestive Tract Immune system of the digestive tract is unique – named the gut-associated lymphoid tissue (GALT) Recent evidence suggests that the most important cells in the initiation of the recognition process are the dendritic cells in the intestinal mucosa They take up dietary proteins and transport them to the mesenteric lymph nodes (MLN) Differentiation of the T cells takes place in the MLN

11. 11 Oral Tolerance In most cases this results in education of the T cells to not respond to that food protein when it enters via the oral route – called oral tolerance Contrasts with the active immune responses needed to protect the gut against continual bombardment by invading pathogens and their products (toxins, etc)

12. 12 Oral Tolerance Also contrasts with the reduced responsiveness to the millions of microorganisms that are permanent residents of the large bowel T cells involved in these processes are designated T reg

13. 13 T cells involved in Oral Tolerance T cell response depends on the type of T helper cell that is activated Latest research indicates that T cells that produce a cytokine called TGF- are important in inducing oral tolerance –Sometimes called Th3 cells ___________________ Strobel and Mowat 2006

14. 14 T cells involved in Oral Tolerance T cells that produce IL-10 may also be involved in tolerance These also regulate immune response to resident microflora, preventing the usual immune inflammatory response to microorganisms

15. 15 T-helper Cell Subclasses There are two subclasses of T-helper cells Type 1: Th1 Type 2: Th2 Cytokines (the control chemicals of the immune system) are released Each subclass produces a different set of cytokines The types of cytokines generated determine the resulting immune response

16. 16 Role of T-helper Cell Subtypes Th1 triggers the protective response to a pathogen such as a virus or bacterium –IgM, IgG, IgA antibodies are produced Th2 is responsible for the IgE-mediated hypersensitivity reaction (allergy) –IgE antibodies are produced

17. 17 Allergic Sensitization Cytokines associated with Th1 (protective) response are predominantly: –INF- –INF- –IL-2 Cytokines associated with allergic (Th2) response are predominantly: –IL-4 –IL-13

18. 18 Antigen- presenting cell Th0 Antigen Th1 Th2 IL-2 IL-3 IL-4 IL-5 Il-13 INF GM-CSF Il-2 Il-3 IFN GM-CSF Il-3 Il-4 Il-5 Il-13 GM-CSF ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Allergens Viruses and Bacteria MHC Class II White blood cells aid the immune system in recognizing foreign proteins T helper ( CD4+) cells respond T helper cells produce characteristic cytokines Specific cytokines determine which response takes place: Th1 = protection Th2 = allergy IgE IgG Immunological Pathways to Protection, Allergy, or Oral Tolerance Receptor Oral Tolerance Transport to thymus TGF- β1 IL-10 Th3 Tr1 Anergy: No immune response CD4+CD25+T reg

19. 19 Th1 Th2 Interactions Factors promoting: Th1 - Bacterial and viral infections - Maturation of the immune system Th2 - Parasite infestations - Immature immune system

20. 20 Th1 Th2 Interactions Factors promoting: Th1 - Bacterial and viral infections - Maturation of the immune system - Antigen tolerance Th2 - Parasite infestations - Immature immune system - Sensitization to antigen Contributing factors: - Genetic inheritance - Early exposure to allergen - Increased antigen uptake -leaky gut

21. 21 Th1 Th2 Interactions Under certain circumstances (eg eczema) Th2 cytokines suppress Th1 cell activity Under certain circumstances (eg eczema) Th2 cytokines suppress Th1 cell activity This causes a decrease in the level of immune protection against microorganisms This causes a decrease in the level of immune protection against microorganisms As a result, infection by normally harmless skin bacteria can occur As a result, infection by normally harmless skin bacteria can occur

22. 22 Th1 Th2 Interactions In contrast, Th1 activity may suppress Th2 response In contrast, Th1 activity may suppress Th2 response Infection with some common childhood illnesses may suppress allergy - the hygiene theory Infection with some common childhood illnesses may suppress allergy - the hygiene theory Certain microorganisms in the large bowel (the resident microflora) can influence the Th1/Th2 balance – role for probiotics? Certain microorganisms in the large bowel (the resident microflora) can influence the Th1/Th2 balance – role for probiotics? Latest research indicates a possible role for a new cytokine IL-18 in Th1/Th2 balance Latest research indicates a possible role for a new cytokine IL-18 in Th1/Th2 balance ____________________ Cebeci et al August 2006

23. 23 IgE-Mediated Allergy Intracellular Granules are Released

24. 24 Many Inflammatory Chemicals are Released in the Allergic Reaction Preformed: –Histamine –Enzymes –Chemo-attractants Newly formed –Prostaglandins –Leukotrienes Each chemical has a different effect on tissues: The allergic response is the combined effect of them all

25. 25 Action of Inflammatory Mediators on Tissues: Histamine Action of Inflammatory Mediators on Tissues: Histamine Vasodilation {blood vessels widen} Swelling of tissues Increased vascular permeability {blood vessels become leaky} –angioedema (swelling) –rhinitis (stuffy nose) –rhinorrhea (runny nose) –urticaria (hives) –otitis media (earache) ItchingFlushingReddening Antidote: Antihistamines: Block receptors for histamine on reactive cells Block receptors for histamine on reactive cells

26. 26 Priority Food Allergens In Canada Peanuts Tree nuts (almonds, Brazil nuts, cashews, hazelnuts (filberts), macadamia nuts, pecans, pinenuts, pistachios, walnuts) Sesame seeds MilkEggsFish Shellfish (e.g. clams, mussels, oysters, scallops and crustaceans (e.g. crab, crayfish, lobster, shrimp) ) SoyWheatSulphites These Priority Allergens account for more than 95% of severe adverse reactions related to food allergens

27. 27 Additional Factors Involved in Symptoms of Food Sensitivity Increased permeability of the digestive tract Increased permeability of the digestive tract (leaky gut) (leaky gut) –Inflammation: InfectionAllergy Autoimmune disease Other diseases –Immaturity (in infants) –Alcohol consumption Physical exertion: Exercise-induced anaphylaxis

28. 28 Additional Factors Involved in Symptoms of Food Sensitivity Stress Eating several different allergenic foods at the same time Other allergies occurring at the same time (e.g. hay fever, asthma)

29. 29 Classification of Food Allergens Classification of Food Allergens Class 1: –Direct sensitization via the gastrointestinal tract after ingestion – Water-soluble proteins or glycoproteins – Stable to: Heat (cooking) Heat (cooking) Proteases (digestive enzymes) Proteases (digestive enzymes) Acid (gastric acid) Acid (gastric acid) – Many are lipid transfer proteins ____________ Sampson 2003

30. 30 Classification of Food Allergens Class 2: –Indirect sensitization by inhalation of air-borne allergen –Cross-reaction to foods containing structurally identical proteins –Heat labile –Many are pathogenesis-related proteins produced when a plant is under stress

31. 31 Oral Allergy Syndrome (OAS) OAS refers to clinical symptoms in the mucosa of the mouth and throat that: Result from direct contact with a food allergen In an individual who also exhibits allergy to inhaled allergens. Usually pollens (pollinosis) are the primary allergens Pollens usually trigger rhinitis or asthma Occurs most frequently in adults

32. 32 Oral Allergy Syndrome Characteristics Inhaled pollen allergens sensitize tissues of the upper respiratory tract Tissues of the respiratory tract are adjacent to oral tissues, and the mucosa is continuous Sensitization of one leads to sensitization of the other OAS symptoms are mild in contrast to primary food allergens and occur only in and around the mouth and in the throat

33. 33 Oral Allergy Syndrome The foods cause symptoms in the oral cavity and local tissues immediately on contact: – Swelling – Throat tightening – Tingling – Itching – Blistering Foods most frequently associated with OAS are mainly fruits, a few vegetables, and nuts

34. 34 Oral Allergy Syndrome Allergens Pollens and foods that cause OAS are usually botanically unrelated Occurs most frequently in persons allergic to birch and alder pollens Also occurs with allergy to: – Ragweed pollen – Mugwort pollen – Grass pollens

35. 35 Oral Allergy Syndrome Cross-reacting allergens Birch pollens with: –Apple –Stone Fruits (Apricot, Peach, Nectarine, Plum, Cherry) –Kiwi Fruit –Orange - Peanut- Almond –Melon - Hazelnut- Walnut –Watermelon - Carrot- Anise –Potato - Celery- Caraway seed –Tomato - Parsnip –Green pepper- Parsley –Cumin - Beans –Coriander - Peas –Dill - Lentils –Sunflower seed- Soy

36. 36 Oral Allergy Syndrome Cross-reacting allergens Ragweed pollen with: –Banana –Cantaloupe –Honeydew –Watermelon –Other Melons –Zucchini (Courgette) –Cucumber

37. 37 Expression of OAS Symptoms Expression of OAS Symptoms Oral reactivity to the food significantly decreases when food is cooked Reactivity of the antigen depends on ripeness –Antigen becomes more potent as the plant material ages People differ in the foods which trigger OAS, even when they are allergic to the same cross-reacting pollens –Foods contain an antigen that is structurally similar to the allergenic pollen, but not all people will develop OAS to all foods having that antigen

38. 38 Identification of Foods Responsible for OAS Symptoms Skin tests will identify the allergenic plant pollen Skin testing has not been successful in identifying persons who react to cross-reacting food antigens –Plant antigens are unstable and do not survive the process of antigen preparation –Crushing plant material leads to release of phenols and degradative enzymes Prick + prick technique are more reliable than standard skin tests –Lancet is inserted in raw fruit or vegetable, withdrawn and then used to prick the persons skin

39. 39 Latex-Fruit Syndrome Allergy to latex often starts as: Contact allergy to a latex protein, usually through: – Abraded (non-intact) skin – Mucous membrane – Exposed tissue (e.g. during surgery) Inhalant allergy: –Inhaled powder from latex gloves

40. 40 Latex Allergy Cross-reacting allergens As antigen comes into contact with immune cells, repeated exposure leads to IgE mediated allergy Proteins in foods with the same structure as proteins in latex trigger the same IgE response when they are eaten In extreme cases can cause anaphylactic reaction

41. 41 Latex Allergy Related foods Examples of foods that have been shown to contain proteins similar in structure to latex: –Banana - Mango - Tomato –Citrus Fruits - Melon - Celery –Kiwi Fruit - Pineapple - Avocado –Fig - Papaya - Tree Nuts –Passion Fruit - Peach - Chestnut –Grapes - Potato- Peanut

42. 42 Common allergens in unrelated plant materials OAS and latex allergy are examples of conditions in which common antigens, expressed in botanically unrelated plants, are capable of eliciting a hypersensitivity reaction In practice, when a specific plant food elicits an allergic response, foods in the same botanic family rarely elicit allergy

43. 43 Legume Allergy There is no evidence to support the thinking that peanut-allergic individuals should avoid all legumes Avoidance of legumes such as soy, chick peas, lentils, beans, peas, licorice, carob, and all other members of the Leguminoceae family, to which peanut belongs, is only necessary when allergy to the individual foods has been identified _________________________ Bernhisel-Broadbent et al 1989

44. 44 Legume Allergy In laboratory experiments, cross- reactivity between peanut and soy is quite frequent, but in clinical trials, the cross-reactivity is quite uncommon –One study reports only 2 out of 41 peanut- allergic patients reacted mildly to other members of the legume family

45. 45 Peanut and Soy Allergy Increase in the incidence of soy allergy, especially in children Soy and peanuts contain a similar allergen May be the result of exposure to the allergenic protein, in the form of soy- based infant formulas, in early infancy when the child is at highest risk for allergic sensitization ____________ Lack et al 2003

46. 46 Peanut and Soy Allergy Exposure to the soy allergen in infant formula could prime the childs immune system to respond to the peanut allergen, even when he or she shows no signs of allergy to soy As a result, the child could exhibit allergic symptoms on an apparent first exposure to the peanut

47. 47 Tree Nut Allergy Tree nuts are botanically unrelated to peanuts It is not necessary to avoid tree nuts such as hazelnuts (filberts), Brazil nuts, walnuts, pecans, almonds, macadamia nuts, pine nuts, pistachios, etc. unless the individual has an allergy to them

48. 48 Tree Nut Allergy Nuts in a nut mixture are very difficult to distinguish from each other Risk of tree nuts, especially nut mixtures, to contain, or to be contaminated by peanuts A person who has demonstrated allergy to peanuts is usually advised to avoid nuts of all types in the interests of safety

49. 49 Take-Home Message There are many different processes involved in the expression of food allergy No single lab test will identify the foods responsible for symptoms The presence of allergen-specific IgE does not predict the response when the food is eaten Elimination and challenge is the only way to identify the foods responsible for symptoms

50. 50 Take-Home Message When the culprit food(s) have been identified avoidance of the food is essential Discourage unnecessary food restrictions Client must be provided with: –Information about which foods must be avoided –Resources to recognize allergen in manufactured and prepared foods –Meal plans to supply complete balanced nutrition from alternate sources

51. 51 Take-Home Message New research indicates that only the foods causing symptoms should be avoided When there are no longer any clinical signs of allergy (symptoms) after consumption of the food, tolerance has occurred In order to maintain tolerance the food should be eaten regularly

52. 52 Take-Home Message The more foods that are tolerated, the more foods will be tolerated – bystander effect of TGF- The more foods that are tolerated, the more foods will be tolerated – bystander effect of TGF- Unnecessary and prolonged avoidance of a food may result in sensitization when the food is eaten