In nature, there are proteins in various pollen, fruits, cereals, nuts, spices, and insect venoms that contain sugar structures that can be recognised by the human immune system as foreign and may elicit the production of IgE antibodies.
Nearly 30% of allergic individuals have IgE antibodies against these sugar structures. (1, 2, 3) They neither predict the development of clinical symptoms upon allergen exposure, nor are they associated with disease severity. (4, 5)
However, IgE antibodies directed against these sugar structures, also known as CCDs (Cross-reactive Carbohydrate Determinants), can lead to falsely elevated test results that give a misleading impression of clinically relevant polysensitisation and lead to inaccurate diagnosis. Therefore, it is essential to consider the possible presence of CCD-specific IgE antibodies in a patients’ serum sample.
Absorption of these sIgE CCD antibodies leads to results with higher clinical specificity. (6, 7)
The ALEX² Allergy Xplorer is a modern in-vitro molecular allergy diagnostic test that integrates a CCD blocking agent to absorb CCD-directed antibodies.
The test eliminates false-positive test results due to CCD interference and avoids clinically irrelevant results. Thus, CCD blocking is integrated by default in every ALEX² test kit without the need for an additional incubation step and is essential for accurate in-vitro allergy testing.
Interested in a clinical case showing the importance of CCD blocking? Read about the case of 19-year-old Eva and find out more.
References
- Mari A. IgE to cross-reactive carbohydrate determinants: analysis of the distribution and appraisal of the in vivo and in vitro reactivity. Int Arch Allergy Immunol 2002; 129:286–295 https://doi.org/10.1159/ 000067591 PMID: 12483033 14.
- Holzweber F, Svehla E, Fellner W, Dalik T, STubler S, Hemmer W, et al. Inhibition of IgE binding to cross-reactive carbohydrate determinants enhances diagnostic selectivity. Allergy 2013; 68:1269–1277 https://doi.org/10.1111/all.12229 PMID: 24107260
- Hemmer W. Human IgE antibodies against cross-reactive carbohydrate determinants. In: Kosma P, Muller-Loennies S (Eds.), Anticarbohydrate Antibodies. From Molecular Basis to Clinical Application. Springer Wien, 2012, pp. 181–202
- Ahrezem O, Ibanez MD, Lopez-Torrejon G, Sanchez-Monge R, Sastre J, Lombardero M, et al. Orange germin-like glycoprotein Cit s 1: an equival allergen. Int Arch Allergy Immunol 2006; 139:96–103 https://doi.org/10.1159/000090384 PMID: 16357490 11.
- Malandain H, Giroux F, Cano Y. The influence of carbohydrate structures present in common allergen sources on specific IgE results. Eur Ann Allergy Clin Immunol 2007; 39:216–220. PMID: 18236996 12. Altmann F. Coping with cross-reactive carbohydrate determinants in allergy diagnosis. Allergo J Int 2016; 25:98–105 https://doi.org/10.1007/s40629-016-0115-3 PMID: 27656353
- Sinson E, Ocampo C, Liao C, Nguyen S, Dinh L, Rodems K, et al. Cross-reactive carbohydrate determinant interference in cellulose-based IgE allergy tests utilizing recombinant allergen components. PLoS One 2020;15:e0231344.
- Hemmer W, Altmann F, Holzweber F, Gruber C, Wantke F, Wohrl S. ImmunoCAP cellulose displays cross-reactive carbohydrate determinant (CCD) epitopes and can cause false-positive test results in patients with high anti-CCD IgE antibody levels. J Allergy Clin Immunol 2018;141:372–81.