Inhibition of IgE binding to cross-reactive carbohydrate determinants enhances diagnostic selectivity

Allergy. 2013 Oct;68(10):1269-77. doi: 10.1111/all.12229. Epub 2013 Sep 21.

Abstract

Background: Allergy diagnosis by determination of allergen-specific IgE is complicated by clinically irrelevant IgE, of which the most prominent example is IgE against cross-reactive carbohydrate determinants (CCDs) that occur on allergens from plants and insects. Therefore, CCDs cause numerous false-positive results. Inhibition of CCDs has been proposed as a remedy, but has not yet found its way into the routine diagnostic laboratory. We sought to provide a simple and affordable procedure to overcome the CCD problem.

Methods: Serum samples from allergic patients were analysed for allergen-specific IgEs by different commercial tests (from Mediwiss, Phadia and Siemens) with and without a semisynthetic CCD blocker with minimized potential for nonspecific interactions that was prepared from purified bromelain glycopeptides and human serum albumin.

Results: Twenty two per cent of about 6000 serum samples reacted with CCD reporter proteins. The incidence of anti-CCD IgE reached 35% in the teenage group. In patients with anti-CCD IgE, application of the CCD blocker led to a clear reduction in read-out values, often below the threshold level. A much better correlation between laboratory results and anamnesis and skin tests was achieved in many cases. The CCD blocker did not affect test results where CCDs were not involved.

Conclusion: Eliminating the effect of IgEs directed against CCDs by inhibition leads to a significant reduction in false-positive in vitro test results without lowering sensitivity towards relevant sensitizations. Application of the CCD blocker may be worthwhile wherever natural allergen extracts or components are used.

Keywords: CCDs; IgE; allergens and epitopes; cross-reactive carbohydrates; false positives.

MeSH terms

  • Adolescent
  • Adult
  • Antibody Specificity / immunology
  • Carbohydrates / immunology*
  • Child
  • Child, Preschool
  • Cross Reactions / drug effects
  • Cross Reactions / immunology*
  • Glycopeptides / chemistry
  • Glycopeptides / pharmacology
  • Humans
  • Hypersensitivity / diagnosis*
  • Hypersensitivity / immunology*
  • Immunoglobulin E / immunology*
  • Male
  • Middle Aged
  • Protein Binding / drug effects
  • Protein Binding / immunology
  • Sensitivity and Specificity
  • Skin Tests / methods
  • Skin Tests / standards
  • Young Adult

Substances

  • Carbohydrates
  • Glycopeptides
  • Immunoglobulin E