Food Allergies Whats New in Clinical Community School

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

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 (<2%) Prevalence of peanut allergy doubled in American children younger than 5 years of age in the past 5 years 2

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 3

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

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 induce tolerance of foods 5

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

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 7

Antigen Recognition § 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 helper cells (CD 4+ subclass) (Th) identify the foreign protein as a “potential threat” 8

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 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 9

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 10

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) 11

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 Treg 12

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 Th 3 cells __________ Strobel and Mowat 2006 13

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 14

T-helper Cell Subclasses There are two subclasses of T-helper cells Type 1: Th 1 Type 2: Th 2 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 15

Role of T-helper Cell Subtypes Th 1 triggers the protective response to a pathogen such as a virus or bacterium – Ig. M, Ig. G, Ig. A antibodies are produced Th 2 is responsible for the Ig. E-mediated hypersensitivity reaction (allergy) – Ig. E antibodies are produced 16

Allergic Sensitization Cytokines associated with Th 1 (protective) response are predominantly: – INF- – IL-2 Cytokines associated with allergic (Th 2) response are predominantly: – IL-4 – IL-13 17

Immunological Pathways to Protection, Allergy, or Oral Tolerance Antigen- presenting cell T helper ( CD 4+) cells respond Receptor Antigen Th 0 MHC Class II IL-2 IL-3 IL-4 IL-5 Il-13 INF GM-CSF Viruses and Bacteria Il-2 Il-3 IFN GM-CSF Ig. G Specific cytokines determine which response takes place: Th 1 = protection Th 2 = allergy Allergens White blood cells aid the immune system in recognizing foreign proteins Th 1 Th 2 Il-3 Il-4 Il-5 Il-13 GM-CSF T helper cells produce characteristic cytokines Transport to thymus Ig. E ---------------------------------------------------------------------------------------- IL-10 TGF-β 1 Th 3 CD 4+CD 25+Treg Oral Tolerance Tr 1 Anergy: No immune response 18

Th 1 Th 2 Interactions Factors promoting: Th 2 - Parasite infestations - Immature immune system Th 1 - Bacterial and viral infections - Maturation of the immune system 19

Th 1 Th 2 Interactions Factors promoting: Th 2 - Parasite infestations - Immature immune system - Sensitization to antigen Th 1 - Bacterial and viral infections - Maturation of the immune system - Antigen tolerance Contributing factors: - Genetic inheritance - Early exposure to allergen - Increased antigen uptake -“leaky gut” 20

Th 1 Th 2 Interactions § Under certain circumstances (eg eczema) Th 2 cytokines suppress Th 1 cell activity § This causes a decrease in the level of immune protection against microorganisms § As a result, infection by normally harmless skin bacteria can occur 21

Th 1 Th 2 Interactions § In contrast, Th 1 activity may suppress Th 2 response § Infection with some common childhood illnesses may suppress allergy - the “hygiene theory” § Certain microorganisms in the large bowel (the resident microflora) can influence the Th 1/Th 2 balance – role for probiotics? § Latest research indicates a possible role for a new cytokine IL-18 in Th 1/Th 2 balance __________ Cebeci et al August 2006 22

Ig. E-Mediated Allergy Intracellular Granules are Released 23

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 24

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) Itching Flushing Reddening Antidote: Antihistamines: Block receptors for histamine on reactive cells 25

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

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

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) 28

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

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 30

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 31

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 32

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 33

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 34

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 35

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

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 37

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 person’s skin 38

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 39

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

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

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 42

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 43

Legume Allergy In laboratory experiments, crossreactivity 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 peanutallergic patients reacted mildly to other members of the legume family 44

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 soybased infant formulas, in early infancy when the child is at highest risk for allergic sensitization ______ Lack et al 2003 45

Peanut and Soy Allergy Exposure to the soy allergen in infant formula could prime the child’s 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 46

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 47

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 48

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 Ig. E does not predict the response when the food is eaten Elimination and challenge is the only way to identify the foods responsible for symptoms 49

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 50

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 51

Take-Home Message 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 52