Specific IgE to cross-reactive carbohydrate determinants strongly affect the in vitro diagnosis of allergic diseases

Background: Cross-reacting carbohydrate determinants (CCDs) are antigenic s tructures shared by allergenic components from taxonomically distant source s. The case history of a patient with a great discrepancy between skin test and specific IgE results led us to investigate the role of these determina nts in his specific case and in an allergic population. Objective: We sought to determine the role of CCDs in causing false-positiv e and clinically irrelevant results in in vitro tests. Methods: The involvement of CCDs was studied by specific IgE inhibition by using glycoproteins with a known carbohydrate structure. Direct and inhibit ion assays were performed by commercially available systems, in-house ELISA , and the immunoblotting technique. The binding to the periodate-oxidated c arbohydrate structure of glycoproteins and allergenic extracts was also eva luated. A comparative study between skin test and specific IgE responses to the antigens studied was carried out in 428 consecutive allergic subjects. Results: All the tests performed suggested that cross-reacting carbohydrate epitopes were the cause of false-positive specific IgE results in one of t he commercial systems and the high reactivity in all the solid-phase in vit ro tests. None of the crossreacting carbohydrate allergens yielded a positi ve skin test response. Periodate treatment caused variable degrees of reduc tion of IgE binding to the different antigens studied, indicating that CCDs played a different role in each of them. About 41% of patients allergic to pollen had specific IgE for a glycoprotein, without a positive skin test r esponse to the same molecule. Conclusions: CCDs must be taken into account when evaluating the clinical r elevance of positive results in in vitro specific IgE assays, at least in t he diagnosis of patients with pollen allergy, Commercial systems should be carefully assessed for the ability to detect specific IgE for carbohydrate determinants to avoid false-positive or clinically irrelevant results.