Multiple Allergen ImmunoCAP (fx5)

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• Phadiatop is a test for atopic sensitization to common inhalants in people with respiratory symptoms
   
• A mix of animal epithelia is used for screening of people with perennial indoor problems potentially caused by pets.
   
• A multi-grass pollen allergen can confirm summer hay fever

The multi-food allergen fx5 is special in the sense that, in addition to its function as a food allergen panel representing the foods included, it is also a test for atopic sensitization in children younger than about three years. The basis for this is:

• The composition of allergens include the most common food allergens of young age (Fig.1).
   
• Atopic sensitization commonly starts at very young age, the main sensitizers being food allergens like egg, milk, etc., causing eczema, gastrointestinal problems, and sometimes asthma.
   
• Sensitization by inhalant allergens is uncommon in the very young child. 

Fig. 1. The protein contents of different raw materials used in fx5 and the final protein mixture. SDS PAGE electrophoresis, 12,5% homogeneous gel, silver staining.

Sample no. 5 and 6 molecular weight markers
Sample no. 7 egg white (f1)
Sample no. 9 milk (f2)
Sample no. 11 fish (f3)
Sample no. 13 wheat (f4)
Sample no. 15 peanut (f13)
Sample no. 17 soya bean (f14)
Sample no. 19 fx5 protein mixture
Sample no. 20 and 21 molecular weight markers

The evolution of allergic disease with increasing age has been described by several investigators (1-6)from different corners of the world. Fig. 2 shows one example, see also (7). The studies show differences in the allergen specificity and the kinetics of the developing disease, depending on the type and intensity of exposure to inhalant allergens, but not in the general shift from food to inhalants or from skin and gastrointestinal symptoms to respiratory problems.

Fig. 2. Food and inhalant specific IgE antibodies in Swedish children. Data from N Sigurs et al (3)

It is obvious from the data presented in Table I that, although fx5 is highly efficient (about 90 %) as an indicator of atopic disease at young age, the sensitivity of the test drops as the antibodies to egg and/or milk decrease or disappear. However, not all patients grow out of their hypersensitivity to food allergens. Allergy to peanut, hazelnut, and probably also to other foods, often develops early and seems to stay for life (3,8). Also, teenagers and young adults with known inhalant allergies sometimes add food allergy to their repertoire. In cases where clinical history is not indicative of allergens involved, fx5 should be one of the reagents used also for adult patients.

The efficiency of fx5 as compared to testing with the six ingredient allergens separately is in the same range as has been shown for other multi-allergens, including Phadiatop®, i.e. about 90 % (Table 1). Calculated sensitivity varies as discussed above with the type of clinical question asked and with patient age.

Table 1.
Examples of the effect of patient selection on sensitivity and specificity

1. Karolinska Hospital 1994
   
   168 samples out of about 900 consecutive samples tested with fx5 over a period of about five months were also tested with f13 peanut and f14 soy because of request from physician.
   
   10 were positive to fx5. 4 of these were positive to f13 and 3 positive to f14
   
   158 were negative to fx5. 15 of these were positive to f13 (9.5%) and 7 positive to f14 (4.4 %)
   
   Conclusion : More than 90 % of the negatives were correctly negative, i.e. no antibodies could be detected by the single allergen.
   
   An immunoblotting study with five of the sera with discrepant results showed that their antibody patterns were either monospecific or very limited.
    
    
2. An in house study (October 97) on 328 sera selected for positive results to f13 and/or f14.
   
   All the sera were tested with fx5 and 298/328 (90.9 %) showed positive results.
   
   293/321 of the f13 positive sera were positive with fx5 (91.3%)
   
   278/297 of the f14 positive sera were positive with fx5 (93.6%)
   
   Conclusion : The sensitivity of fx5 for the detection of IgE antibodies to peanut and soy is higher than 90%.
    
    
3. A study in Irish Republic during March 1998. 104 sera from patients with suspected food allergy having negative fx5 results were collected in a routine laboratory. The patients were adults and children born 1920-1996. 398 tests for specific IgE antibodies were performed against 4 of the food allergens (f1, f2, f4, f13) represented in fx5.
   
   Only 11 tests (2.8 %) showed positive result to an identified allergen in 9 (8.7%) of the 104 patients. In 4 of the 9 cases fx5 was positive when repeated.
   
   Conclusion : Confirmed discrepant results were obtained in only 5/100 cases (5%).
   
   Peanut (f13) was involved in two cases.
   
   The data are in agreement with previous studies showing sensitivity higher than 90%.

References:

1. Rowntree S, Cogswell JJ, Platts-Mills TA, Mitchell EB. Development of IgE and IgG antibodies to food and inhalant allergens in children at risk of allergic disease. Archives of Disease in Childhood 1985; 60: 727-735.
2. Zimmerman B, Forsyth S, Chambers, C. Diagnosis of atopy in young children with mixed allergen RAST discs (pediatric mix and Phadiatop). Alergologia e Inmunologia Clinica 1987;2: 94.
3. Sigurs N et al. Atopy in childhood identified by Phadebas RAST, serum IgE, skin test and Phadiatop. Allergy 1988; 43 Suppl. No 7:8.
4. Saarinen UM, Kajosaari M. Breastfeeding as prophylaxis against atopic disease; prospective follow-up study until 17 years old. The Lancet 1995; 346: 1065-1069.
5. Shibata R. Data from study reported in Ref. 6.
6. Okudaira H et al. Evaluation of a new system for the detection of IgE antibodies (CAP) in atopic disease. Arerugi 1991; 40: 544-554
7. Yman L. Phadiatop, design and performance. Manuscript.
8. Zimmerman B, Forsyth S, Gold M. Highly atopic children: Formation of IgE antibody to food protein, especially peanut. J Allergy Clin Immunol 1989; 83: 764 -770.
9. Zimmerman B, Forsyth S. Diagnosis of allergy in different age groups of children: Use of mixed allergen RAST discs, Phadiatop and Paediatric mix. Clinical Allergy 1988; 18: 581-587.
10. Hochreutener H. Klinik und allergologisch-immunologische Parameter bei 40 Kindern von 0-7 Jahren mit atopischer Dermatitis. Monatsschr Kinderheilkd 1991; 139: 618-625.
11. Andre F, Andre C, Cavagna S. Évaluation du RAST Fx5 dans le diagnostic de l’allergie alimentaire de l’adulte et de l’enfant. Rev. fr. Allergol. 1992; 32: 11-15.
12. Moneret-Vautrin DA, Frémont S, Kanny G, Déjardin G, Hatahet R, Nicolas JP. The use of two multitests fx5 and fx10 in the diagnosis of food allergy in children: regarding 42 cases. Allergie et Immunologie 1995; 27: 2-6.

• References