1. Peanut Allergy Kate Byrne DT204/2 Research and Development

2. What is an allergy?  An allergy occurs as the result of the immune system carrying out a misguided reaction to a foreign substance. It is a misguided reaction due to the fact the foreign substance detected and acted upon by the immune system is usually harmless.  An antigen is a molecule that induces the body to produce antibodies to it. It is an antibody generating molecule.  An allergen is a substance that triggers an allergy. In the case of peanuts allergens include Ara h1, Ara h2, Ara h3, Ara h4, Ara h5, Ara h6, Ara h7, Ara h8, Ara h9, Ara h10 and Ara h11.  A food allergy can be IgE or non IgE mediated.  IgE mediated food allergies account for the majority of food allergies. This allergy type results in an increased production of this antibody and the reaction occurs when an allergenic protein binds to IgE. Compounds such as histamines are released from mast cells in response to this binding.  Non IgE mediated food allergies are T cell mediated. T cells become sensitized on initial exposure to the antigen. On secondary contact, Cytokines are released in response to allergen bound sensitized t cells.  Both allergy types cause inflammation. Figure 1. Image of peanuts (www.mommyish.com)

3. The Peanut Allergy Peanuts are classified as a legume. A peanut is 26% protein. Ara h1, Ara h2, Ara h3 and Ara h6 are considered to be the major allergens. Everyone with a peanut allergy will be sensitive to Ara h2, thus it is the allergen involved in many allergic reactions to peanuts. It is Ara h1 that causes the severe reactions. Peanut allergy is a severe food allergy. It is an IgE mediated food allergy. It is estimated that 0.5% of adults in the UK have a peanut allergy. In children prevalence of this allergy is increased 1.4%. 1 in 70 children having this allergy. A study carried out in 2003 confirmed the mean age of onset of this allergy was between 1-3 year. Development of this allergy in teenagers and older people is rare. One study showed only 8% of peanut allergy developed in teenagers and older people. A study carried out in 2001 confirmed that by the age of 5, 20% of children will outgrow this allergy. Mild allergic symptoms to peanuts include: Tingling in the mouth and lips, swelling of the face, abdominal pain, hives or tightness around the throat. Additional symptoms in a severe case include: Difficulty in breathing, dilation of blood vessels which increases blood flow causing redness of the face, increased heart rate, low blood pressure causing patient to feel faint or collapse – Anaphylaxis. Figure 2. Diagram detailing the symptoms of anaphylaxis (www.medicinenet.com)

4. What causes a peanut allergy?  In a person without a peanut allergy, peanut proteins are prevented from entering the tissues by physiological and immunological barriers in the gut.  In a person with a peanut allergy, peanut allergens enter the gastrointestinal tract and an immune response is employed.  Engulfment of the peanut proteins by APCs results in the signalling of b cells to produce peanut specific IgE.  Peanut specific IgE has high affinity receptors on cells which mediate the binding of this antibody to mast cells in the body’s tissue and basophils in the blood.  This is called sensitization.  Peanut allergens have locations called epitopes to which they use to bind IgE.  This binding initiates the degranulation of mast cells, leukotrienes and platelet activation factor.  The structure of the major peanut allergens – Ara h1, Ara h2, Ara h3, Ara h6 facilitates the binding of IgE thus promoting the cause of peanut allergy.  Heat treatment of peanuts has been proven to increase the allergic properties of peanuts. It increases the allergens ability to bind to IgE by 90 fold. Figure 3. Diagram of the immune systems response to the presence of an allergen (www.gene.com)

5. Methods of Identifying the presence of a peanut allergy:  1. Skin prick test – Nut extract solution is introduced into the epidermis of the skin. Visible formation of ‘wheel and flare’ is a positive result.  Investigation into skin prick testing by Spoirk showed that SPT ≥ 8mm was 100% predictive of peanut allergy in young children and the median age was 3. For children under the age of 2, the required diameter was only ≥ 4mm to ensure 100% specificity to peanut allergy.  2. Medical history – Helpful in situations where test results are inconsistent.  3. Determination of serum peanut-specific IgE – Using ImmunoCAP method.  A study determined that specific IgE greater than 15kUA/L has a 95% predicitive probability for diagnosing peanut allergy and a value of less than 0.35 Kua/L has an 85% predictive probability for ruling out peanut allergy.  4. Medically supervised oral food challenges – Includes both open and blinded challenges. Both highlight if the food ingested induces a reaction or not.  5. Basophil activation tests – Detects surface proteins expression alterations, in response to activation by allergens.  6. Food diary and exclusion diets – Removal of peanuts from the diet to see if symptoms improve, then reintroducing peanuts to see if it leads to a reoccurrence of symptoms. Figure 4. Diagram of skin prick test (www.webmd.com) Figure 5. Diagram of food diary (www.pinterest.com)

6. Commercial and self tests available to detect peanut allergy.  There are many shop-bought tests available today, claiming its use results in the detection of allergies. They include:  Vega testing - claims to be able to detect food allergies by measuring changes in the body’s electrical conductivity. A drop in conductivity on exposure to the peanut, the person is deemed allergic.  Kinesiology testing - claims to be able to detect peanut allergy by studying the body’s muscular strength or weakness.  Hair analysis - claims to be able to detect peanut allergy by investigation of a patients hair  Self tests: Food and drink scan provided by Yorktest Laboratories. It is an at home laboratory kit claiming it can identify food allergies including peanut allergy.  The scientific principles these methods of detection of food allergy are based on are independent and unproven. There is a lack of scientific and clinical evidence supporting these methods of testing.

7. Treatment of peanut allergy:  Peanut allergy cannot be treated.  Recently investigations into sublingual and oral immune therapy have been carried out.  These are potential therapies for patients with food allergy.  Oral immune therapy involves daily administration of peanut allergen mixed with food, gradually increasing the dose.  Sublingual immune therapy involves placing a small drop of the peanut allergen under the tongue. The principle of this is that the allergen interacts with the protolergenic Langerhan cells in the oral mucosa and this supresses the allergic response.  Dietary avoidance and emergency care plans are vital.  In order to avoid accidental consumption or reaction to peanuts, all peanut containing food and drinks must be absent from the diet. Handling, inhaling and cross contamination of peanuts must also be avoided.  This is vital as this allergy is IgE mediated and reactions can be severe.  Reading food labels carefully and inquiring about unpackaged foods Eg. baked goods is essential.  In response to the ingestion of a peanut, treatment is available.  In a very mild reaction antihistamines can be used. They block the effects of histamine.  Adrenaline is used to treat anaphylaxis. It is the first line of treatment. It helps to ease the difficulties in breathing. Figure 6. Diagram of EpiPen (www.sciencebloGs.com)

8. Reference list:  Brostoff, J. and Gamlin, L. (1992) ‘Food Allergy, Mast Cells and IgE’. In: Brostoff J, Gamlin, L (Eds). Food Allergy and Intolerance, 2nd ed. London: Bloomsbury Publishing Limited.  Towell, R. (2009) ‘Peanuts, Legumes, Seeds And Tree Nuts’. In: Skypala, I., and Venter, C (Eds). Food Hypersensitivity. United Kingdom: Blackwell Publishing Ltd.  Zhuang, Y. and Dreskin, S. (2013) ‘Redefining the Major Food Allergies’. Immunol Res, 55(0), pp. 125-134.  Maleki, S, J., Chung, S., Champagne, T., et al. (2000) ‘The Effects of roasting on the allergic properties of peanut proteins’. The Journal of Allergy and Clinical Immunology, 106(4), pp. 763-768. Available from Science Direct [Accessed 29 January 2016].  Santos, F, A., Douiri, A., Becares, N., et al. (2014) ‘Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children’. The Journal of Allergy and Clinical Immunology, 134(3), pp. 645-652. Available from Science Direct [Accessed 29 January 2016].  Patil, S, U., and Shreffler, W, G. (2014) ‘BATing above average: Basophil activation testing for peanut allergy’. The Journal of Allergy and Clinical Immunology, 134(3), pp. 653-654. Available from Science Direct [Accessed 2 February 2016].  Kumar, S., Kumar Verma, A., Das, M., et al (2012) ‘Molecular Mechanisms of Ige Mediated Food Allergy’. International Immunopharmacology, 13(4), pp. 432-439. Available from Science Direct [Accessed 2 February 2016].  Pongdee, T. (2016) American academy of Allergy Asthma and Immunology. Available at: http://www.aaaai.org/conditions-and-treatments/library/allergy-library/oral-food-challenge.aspx [Accessed 6 February 2016]. 

9. Reference list:  Skypala, I. (2009) ‘Triggers of Food Hypersensitivity’. In: Skypala, I and Venter, C (Eds). Food Hypersensitivity. United Kingdom: Blackwell Publishing Ltd.  Gazzola, A. (2007). Institute for Optimum Nutrition. Available at: http://www.ion.ac.uk/information/onarchives/diagnosingallergy [Accessed 11 Feburary 2016] http://www.ion.ac.uk/information/onarchives/diagnosingallergy  Mc Lean-Tooke, A P C., Bethune, CA., Fay, A C., et al. (2003) ‘Adrenalin in the treatment of anaphylaxis: what is the evidence?’ NCBI, 327(7427), 1332-1335. Available from PMC [Accessed 6 February 2016].  Le, U H., Burks, AW. (2014) ‘Oral and sublingual immunotherapy for food allergy’. World Allergy Organisation Journal, 7(1), 31. Available from BioMed Central [Accessed 10 February].  HSE. (2016) Allergy, food. Available at: http://www.hse.ie/eng/health/az/A/Allergy,-food/Causes-of-a-food- allergy.html [Accessed 7 February 2016].http://www.hse.ie/eng/health/az/A/Allergy,-food/Causes-of-a-food- allergy.html  Wood, R A. (2007) ‘Picking On Peanuts: A Potentially Deadly Foe’. In: Wood, R A and Kraynak, J (Eds). Food Allergies for Dummies. Hoboken: Wiley Publishing.  Sun, B., Michael, M., Jiang, M. et al. (2008) ‘Comparison between two commercial immune assays: Dr. Fooke ALLERG-O-LIQ versus Phadia ImmunoCAP system in detecting allergen specific IgE and total IgE values’. Journal of Nanjing Medical University, 22(5), 273-278. Available from Science Direct [Accessed 11 February].  Al-Ahmed, N., Alsowaidi, S. and Vadas, P. (2008) ‘Peanut Allergy: An Overview’. Allergy Asthma and Clinical Immunology, 4(4), 139-143. Available from Science Direct. [Accessed 11 February].  Burks, W. (2003) ‘Peanut allergy: a growing phenomenon’. The Journal of Clinical Investigation, 111(7), 950- 952. Available from NCBI [Accessed 2 February 2016].