Diagnostic Assay Identifies Which Species Patients with Fish Allergy Can Tolerate

Fish allergy is an immune hypersensitivity to proteins found in fish. Symptoms can be either rapid or gradual in onset. The latter can take hours to days to appear. The former may include anaphylaxis, a potentially life-threatening condition which requires treatment with epinephrine.

Diagnostic tests for fish allergy included skin-prick tests and blood antibody tests, which are used to check for the presence of an immune protein called an anti-parvalbumin antibody, which the body produces in response to a fish allergen. If the tests aren’t conclusive, an allergist may recommend an oral food challenge.

Allergy Specialists at the University Hospital St. Pölten (St. Pölten, Austria) and their colleagues investigated whether multiplex immunoglobulin E (IgE) testing reveals potentially tolerated fish through absence of IgE to parvalbumin (PV) and extracts from specific species. Sera from a cohort that comprised 263 patients (median age, 12 years; range, 1-65; 160 of whom were males) from Austria, China, Denmark, Luxembourg, Norway and Spain with a documented clinical history of fish allergy and confirmed sensitization to fish.

The team used a research version of the ALEX2 multiplex IgE quantification assay (Macro Array Diagnostics, Vienna, Austria). Specific IgE to PVs from 10 fish species (nine bony and one cartilaginous), and to extracts from seven species was quantified. The IgE signatures of individual patients and patient groups were analyzed using SPSS and R.

The scientists reported that up to 38% of the patients were negative to cod PV, the most commonly used molecule in fish allergy diagnosis. Forty-five patients (17%) tested negative to PVs, but positive to the respective fish extracts, underlining the requirement for extracts for accurate diagnosis. Between 60% (Spain) and 90% (Luxembourg) of the patients were negative to PV and extracts from ray, a cartilaginous fish, indicating its potential tolerance. Up to 21% of the patients were negative to at least one bony fish species. Of the species analyzed, negativity to mackerel emerged as the best predictive marker of negativity to additional bony fish, such as herring and swordfish.

The team also calculated the probability that all three IgE tests would be negative for a species if tolerance to other species is known. They found patients who are negative for tuna are 92% likely to be negative for ray and swordfish. Patients who are negative for mackerel are 93% likely to be negative for herring and ray and 86% likely to be negative for swordfish.

Tanja Kalic, PhD, and Heimo Breiteneder, PhD, a professor of pathophysiology, both study authors, said, “The most commonly used fish allergen in diagnosis is cod parvalbumin, Gad m 1. In the study up to 38% of fish-allergic patients, depending on country of origin, were negative to this molecule, clearly showing that additional parvalbumins from other fish species are required in order to avoid false-negative testing of patients.”

The authors concluded that parvalbumins and extracts from multiple fish species relevant for consumption should be used in fish-allergy diagnosis, which may help identify potentially tolerated species for individual patients. The study was published on August 21, 2022 in The Journal of Allergy and Clinical Immunology: In Practice.

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