5 | Discussion
In our multicenter study, involving 19 centers scattered throughout Italy, we evaluated the prevalence and the sensitization profile of allergic subjects to crustaceans reactive or not reactive also to mollusks
We confirmed once more (11), that the diagnostics with both the extracts and the molecules currently available in the market is inadequate to detect satisfactorily patients hypersensitive to crustaceans and mollusks. We observed an extreme heterogeneity of results from one patient to another using the common diagnostic approaches, including skin prick testing with commercial extracts, skin testing with fresh material and specific IgE measurements. We previously showed the unreliability of commercial extracts for SPT available on the market due to differences in allergenic proteins concentrations (10), thus potentially leading to confounding results.
The currently available molecular diagnostics for seafood shows two major pitfalls. First, not all allergen molecules are present on the diagnostic platforms and, second, practically all the molecules available derive from crustaceans and none from mollusks. The diagnosis of mollusks allergy is therefore always indirect, based on the presumption of cross-reactivity with crustaceans. Of the 58 shellfish molecules currently registered as allergens by the WHO/IUIS Allergen Nomenclature Sub-Committee, only 8 belong to the mollusks (see Table in the repository). If one considers, for instance, that the tropomyosins from mollusks share no more than 60% amino acid sequence identity with the other allergenic tropomyosins isolated so far from crustaceans, insects, mites, and fish (1), one can easily figure out that this might lead to a failure in the detection of allergic patients (12). A 2018 study showed that in the pacific oyster extract, along with many specific allergens of invertebrates, fish, and mites, can be isolated allergens from other different biological sources such as pollen and fungi, thus prompting interesting scenarios about possible unexpected sources of sensitization(13).
Another interesting point of our study concerns the differences in sensitization profiles observed in the different geographic areas of the country. We detected that in the north sensitization to crustaceans was much more frequent than in the center/south, where in turn sensitization to cephalopods and bivalves was more prevalent. These differences might be the result of different culinary habits between the North (where the way of life is more similar to that in Central and Northern Europe) and the South, where habits are similar to those in other Mediterranean countries such as Greece or Spain(8). These geographical differences could also underlie different sensitization mechanisms according to different environmental exposures (11). This point needs to be addressed in future studies.
The finding of three single patients who were mono-reactors to bivalves (both oyster and mussel), suggests that primary sensitization to mollusks is possible, albeit being an extremely rare event, sometimes associated with sensitization also to house dust mites (14). A study designed to verify whether reactivity is always secondary to sensitization to mite allergens should be carried out, focusing attention on a pediatric-only population.
Objective limitations of the study are the absence of oral food challenge in patient selection, which was made only on the anamnestic data, and the use of heterogeneous commercial preparations, both forin vivo and in vitro diagnostics, where it is not always declared. by the producers, the type of crustacean, prawn or shrimp used to prepare the extract.
In conclusion, this study clearly shows the following: (i) current diagnostic methods are inadequate to predict cross-reactivity between crustaceans and mollusks due to the lack of specific mollusks allergens and because these are only partially cross-reactive to crustacean homologue proteins; (ii) the detection of mollusks hypersensitivity must still rely on skin tests with fresh material (and oral challenges where possible); (iii) clinically, there is no need to exclude a priori mollusks from shrimp allergic patients’ diet, unless the available diagnostic instruments support such decision; (iv) albeit rarely, primary sensitization to mollusks seems possible although the incomplete spectrum of shrimp allergens does not allow us to exclude that shrimp acts as primary sensitizer also in those few cases.