Introduction
Fish is a highly valuable and healthy food; however, it is among the most common foods that elicit IgE-mediated allergy. Over 90% of fish-allergic patients are sensitized to the major allergen beta-parvalbumin (PV), and for the last decades the cross-reactivity among PVs from various fish species was considered a hallmark of fish allergy.1,2 Recent studies indicated that the real-life situation is far more complex. The prevalence of fish-allergic patients with a broad or limited cross-reactivity to various species was recently estimated to be 70% and 30%, respectively.3We previously demonstrated low IgE-reactivity to the alpha-PV from thornback ray, a cartilaginous fish, and oral tolerance of this fish by the majority of patients sensitized to bony fish beta-PVs.4 In that study, 18 patients from Luxembourg were analyzed. Future studies investigating the tolerance of ray in larger multinational cohorts remained to be performed. Certain bony fish species may also be tolerated by patients sensitized to only one fish species.5
Precise diagnosis of fish allergy and identification of tolerated species is challenging due to the large number of fish species consumed worldwide, their varying allergen content, differences in allergenicity of alpha- and beta-PVs, and different fish preparation and processing methods.6 Besides the PV, additional allergens, heat stable or not, may also be implicated.7 Clinicians face the challenge to precisely determine tolerated versus symptom-eliciting species for each individual, as performing food challenges (FC) with multiple species and differently processed fish is nearly impossible. Patients with confirmed fish sensitization are routinely advised to strictly avoid all fish, which is often unnecessary. Hence, there is an unmet need to improve in vitrodiagnostics to reduce the number of required FCs.8 For improved in vitro diagnostics, the complementary use of purified natural or recombinant allergens and whole extracts should be considered. Purified allergens overcome the problem of low abundance of some allergens in aqueous extracts.9,10 Whole extracts contain multiple allergens and may be used in raw or heated versions, which may be of different diagnostic value due to changes in allergenic properties of some allergens upon thermal processing.11,12 Multiplex technologies allow the simultaneous quantification of serum IgE specific for individual allergens and whole extracts from multiple species.13
This is the first study which investigates IgE sensitization to PVs from 10 fish species, along with heated and raw fish extracts, using a large multinational cohort (n=263) of fish-allergic patients from 6 countries (Austria, China, Denmark, Luxembourg, Norway and Spain). This study setup allowed us to observe differences in sensitization patterns among individuals with different exposures and eating patterns. The selected species covered various fish families important for human consumption. Up to 90% of the patients, depending on the country, showed no IgE to PV and extracts from ray, while up to 21% tested negative for some of the bony fish species. For certain patients and species, IgE to extracts was higher than to PVs, demonstrating the importance of individual allergens, but also of extracts for accurate diagnosis.