Inhibition of cross-reactive carbohydrate determinants (CCDs) enhances the accuracy of in vitro allergy diagnosis

Background: Cross-reactive carbohydrate determinants (CCDs) as they occur on natural allergens from plants and insects influence the measurement of antigen-specific IgE-antibodies in the context of in vitro allergy diagnosis. When positive results are based solely on the reaction of CCDs with anti-CCD IgE, results must be rated as false-positive. A generally applicable solution to this problem has not yet been presented. Methods/Patients: Sera of patients for whom an assumed allergy should be verified or ruled out were tested with three methods for specific IgE determination (a multiallergen teststrip format, a single allergen test and an allergen-component array) in the absence and presence of a novel, semi-synthetic CCD-blocker. The study was not prospective and for many patients unequivocal clinical data were missing; the data section thus focusses on few, well-defined patient sera. Results: More than 20% of all patients were tested positive for IgE-anti-CCD antibodies and hence against a multitude of similarly glycosylated allergen extracts in a strip-based multiallergen test. Incubation of these positive sera with the CCD-blocker led to significant reductions of read-out values and in many cases to negative test results. The inhibitory efficiency was highest for the allergen strip test and for the component array. Results remained positive for relevant allergens for which a true sensitization had been indicated by skin tests or other means. The CCD-blocker did not alter the read-outs for unglycosylated allergens or – with CCD-negative sera – for all allergens. Conclusion: Elimination of CCD-specific IgE antibodies by means of a synthetic CCD-blocker drastically reduced the number of false-positive in vitro test results without compromising the sensitivity for relevant IgE interactions. Thus, the herein described CCD-blocker constitutes a valuable tool for increasing the test specificity of routine in vitro allergy diagnosis.