1. Literature support Test chart for the use of ImmunoCAP ® Allergen components Suspicion of fruit allergy Risk for severe reactions?

2. Fruit: neg Pru p 3: neg Very low risk for severe reactions to fruit Low risk for severe reactions to fruit Recommendations for further testing Risk grading: Pru p 1 (f419) Pru p 4 (f421) CCD (Ro214) Fruit: pos Pru p 3: neg Fruit: pos Pru p 3: pos Risk for severe reactions to fruit Fruit allergen + Pru p 3 (f420) Test with ImmunoCAP ® Allergen Suspicion of fruit allergy Is it allergy? Risk for severe reactions?

3. Suspicion of fruit allergy Is it allergy? Risk for severe reactions? Pru p 3 – ImmunoCAP ® f420 rPru p 3 Often associated with systemic and more severe reactions in addition to Oral Allergy Syndrome (OAS). Stable to heat and digestion, risk for reactions also to cooked food. A marker for sensitization to fruit LTP (Lipid Transfer Protein). Pru p 1 – ImmunoCAP ® f419 rPru p 1 Often associated with local symptoms such as OAS. A marker for birch-pollen related cross-reactions to fruit. A heat labile protein, cooked food is often tolerated. A marker for sensitization to fruit PR-10 proteins. Pru p 4 – ImmunoCAP ® f421 rPru p 4 Seldom associated with clinical symptoms but may cause demonstrable or even severe reactions in a minority of patients. Present in plants and plant derived foods, associated with a broad spectrum of cross-reactions. A marker for sensitization to profilins. CCD (MUXF3) – ImmunoCAP ® Ro214 MUXF3 Rarely associated with clinical symptoms. A marker for sensitization to cross-reactive carbohydrate determinants (CCD). Present in all plants. References: Asero R et al. J Allergy Clin Immunol 2003;112:427-32, Asero R, Int Arch Allergy Immunol 2005; 138:1-11, Sicherer S, J Allergy Clin Immunol 2001; 108:881-90

4. References Asero R. Review - Plant Food Allergies: A Suggested Approach to Allergen-Resolved Diagnosis in the Clinical Practice by Identifying Easily Available Sensitization Markers Int Arch Allergy Immunol 2005;138:1-11 Asero R et al. Detection of clinical markers in patients allergic to plant-derived foods J Allergy Clin Immunol 2003;112:427-32 Sicherer S. Clinical implications of cross-reactive food allergens J Allergy Clin Immunol 2001;108:881-90

5. Asero R. Review - Plant Food Allergies: A Suggested Approach to Allergen- Resolved Diagnosis in the Clinical Practice by Identifying Easily Available Sensitization Markers Int Arch Allergy Immunol 2005;138:1-11 Systemic reactions (including anaphylaxis and asthma) following intake of Rosaceae fruits* are reported in LPT sensitized patients –These reports are from Spain and Italy –The geographical distribution pattern was confirmed in a study in NL, AT, ES and IT Pollen allergic patients often report OAS after intake of apple and other fruits –A consequence of cross-reactivity to different Bet v 1 homologues in fruits, e.g. Pru p 1, and the birch allergen component Bet v 1 * Apple, pear, peach, apricot, plum, cherry

6. Asero R et al. Detection of clinical markers in patients allergic to plant-derived foods J Allergy Clin Immunol 2003;112:427-32 The risk of severe and potentially life-threatening reactions is relevant if the sensitizing allergen is pepsin resistant and heat stable - as are LTPs Birch-pollen and fruit allergic patients sensitized to labile proteins, as Pru p 1, are at less risk of dramatic reactions after ingestion of the allergenic food –Symptoms usually limited to OAS. –Occasionally, severe reactions are induced after ingestion of foods in pollen- allergic patients. Sensitization to profilin is likely in the presence of OAS to citrus fruits, melons, banana or tomato

7. Sicherer S. Clinical implications of cross-reactive food allergens (A review) J Allergy Clin Immunol 2001;108:881-90 Subjects: 1361 food and pollen allergic patients with OAS, and systemic reactions: –8.7% systemic reactions outside the gastrointestinal tract –3% sometimes systemic reaction without oral symptoms –1.7% anaphylactic chock What distinguish those at risk of severe reactions? Reactions involving specific IgE to LTPs are more likely to be severe! Fruit allergy in absence of allergy to pollen is characterized by specific IgE antibodies detected to: –LTP –Profilin