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.