Sensitization to cross-reactive carbohydrate determinants and the ubiquitous protein profilin: mimickers of allergy

Background During the last decade, evidence has been provided for profilins and cross-reactive carbohydrate determinants (CCDs) to be capable of inducing cross-reactive IgE antibodies with little clinical relevance. Objective To investigate the prevalence of sensitization to CCD and profilin in isolated allergies (birch, timothy grass, house dust mite, pets (cat and/or dog), natural rubber latex (NRL) and hymenoptera venom). To study the contribution of anti-CCD and anti-profilin IgE antibodies as a cause of clinically irrelevant IgE for NRL and apple. Methods For the first part of the study, 100 patients with inhalant allergy, 17 patients with NRL allergy and 40 patients with venom anaphylaxis were enrolled. Diagnosis was based on a questionnaire and a positive IgE determination and skin test for relevant allergen. Patients were identified as sensitized to CCD if they had a negative prick test and positive IgE for the glycoprotein bromelain. Sensitization to profilin was assessed by IgE for rBet v 2 (recombinant birch profilin). For the second part of the study, sera containing IgE against apple (n=82) or NRL (n=38) were classified as true-negative or false-positive according to the presence or absence of an oral allergy syndrome (OAS) or NRL-induced anaphylaxis. In these patients, sensitization to CCD and profilin was evaluated as described above. Results No sensitization to bromelain-type CCD and profilin was found in isolated birch pollen or NRL allergy. In contrast, sensitization to bromelain-type CCD was found in 4/17 patients with isolated grass pollinosis, 5/24 patients with combined pollinosis (birch, timothy, mugwort) and 7/33 patients with venom anaphylaxis. Sensitization to profilin was almost restricted to patients with combined pollen allergy (5/24). In pollen-allergic individuals with a false-positive IgE against NRL the prevalence of sensitization to bromelain-type CCD and profilin IgE was higher than in NRL-allergic patients (P<0.00001 and P=0.0006, respectively). In pollen-allergic individuals with a false-positive IgE to apple, the frequency of sensitization to bromelain-type CCD was higher than in OAS patients (P=0.004). Clinically irrelevant NRL and apple were also found in four and five out of the seven patients sensitized to venom CCD, respectively. In pollinosis, clinically irrelevant NRL and apple IgE antibodies were inhibited by bromelain and recombinant birch profilin, whereas in isolated venom anaphylaxis these antibodies were inhibited by bromelain. Conclusions Patients monoallergic to NRL or birch pollen showed no sensitization to bromelain-type CCD or profilin. Sensitization to profilin and/or bromelain-type CCD, caused by pollen (timothy grass, mugwort) or hymenoptera venom allergens, can elicit false-positive IgE antibodies against NRL and apple.