Immunoglobulin E Sensitization to Cross-Reactive Carbohydrate Determinants: Epidemiological Study of Clinical Relevance and Role of Alcohol Consumption

Abstract

Background: The determinants and biologic significance of IgE-mediated sensitization to cross-reactive carbohydrate determinants (CCDs) are not entirely known. An association between alcohol consumption and CCD sensitization has been reported in studies from Spain and Portugal. Objective: To investigate the relationship of alcohol consumption with CCD sensitization, the role of alcohol dehydrogenase gene polymorphisms, and the clinical consequences of CCD sensitization. Methods: Serum-specific IgE sensitization (≧0.1 kU/l) to a CCD (the N-glycan from bromelain) was assessed in 1,197 adults participating in a population-based study in Copenhagen, Denmark. Alcohol consumption and atopic symptoms (rhinitis, asthma and oral allergy syndrome) were assessed by questionnaire. Examinations included skin prick tests (SPTs), qualitative multiallergen IgE test (Phadiatop®), methacholine bronchial hyperreactivity, eosinophil cationic protein and alcohol dehydrogenase (ADH) gene polymorphisms. Results: Alcohol consumption was significantly associated with CCD sensitization and this was particularly evident in SPT-negative individuals. The fast-metabolizing allele of the ADH1b polymorphism was significantly associated with CCD sensitization in alcohol drinkers. CCD sensitization was associated with atopic symptoms, but associations attenuated markedly when adjusting for SPT reactivity. Conclusions: Our results suggest that the positive association between alcohol consumption and CCD sensitization is universal and not specific to certain populations. The observed association between the ADH1b polymorphism and CCD sensitization may support that alcohol is causally related to the risk of CCD sensitization. The observed association between CCD sensitization and atopic phenotypes did not appear to be independent of SPT reactivity indicating limited significance of CCD sensitization per se.

Minor Interference of Cross-Reactive Carbohydrates with the Diagnosis of Respiratory Allergy in Standard Clinical Conditions

“…However, some inhibition of IgE reactivity to D. pteronyssinus was observed after CCD coincubation in cases with negative SPTs to mites, confirming previous reports [30]. Overall, the prevalence of CCD sensitization was higher in atopic (SPT-positive) than in nonatopic individuals [6,7,8]. This could indicate that the predisposition to develop IgE to environmental substances (or atopy) involves not only protein determinants but also carbohydrates.…”

“…The measuring range is 0.1–100 kU A /l and the manufacturer considers values ≥0.1 kU A /l as positive. Thus, patients with bromelain-sIgE and/or MUXF-sIgE ≥0.1 kU A /l were considered as having CCD sensitization, similar to previous epidemiological studies [6,22]. …”

“…In the general adult population, the prevalence of IgE (≥0.35 kU A /l) to a CCD marker (MUXF, the bromelain-type N-glycan) ranges from 2.1% in an urban population in Denmark [6] to 5.6% in a mostly rural population in Spain [7]. In an allergy clinic in Italy, the prevalence of IgE (>0.4 kU A /l) to bromelain reached 23% [8].…”

“…In an allergy clinic in Italy, the prevalence of IgE (>0.4 kU A /l) to bromelain reached 23% [8]. Risk factors for CCD sensitization include atopy, particularly pollen sensitization [6,7,8,9,10]. The prevalence of CCD sensitization is highest among patients with a Hymenoptera venom allergy, particularly in patients with double (honeybee and wasp) IgE reactivity [11,12,13,14,15].…”

“…From the initial CCD description in 1984 [16], Hymenoptera stings have been suspected as a source of CCD sensitization [15]. Additional factors for sensitization may include alcohol consumption, which increases total IgE levels [17,18,19,20,21] and is consistently associated with CCD sensitization [6,7,22,23]. This study aimed to investigate the prevalence of IgE-mediated CCD sensitization in patients who attended an allergy clinic due to suspicion of respiratory allergy.…”