Diagnostic assay identifies which species patients with fish allergy can tolerate
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Key takeaways:
- Testing requires parvalbumins as well as raw and heated extracts from multiple fish species for the greatest accuracy.
- The IgE of only 22% of the cohort recognized ray parvalbumin, indicating its low allergenicity.
- Up to 21% of patients may tolerate one or more species of bony fish.
Multiplex IgE testing using parvalbumins and extracts from multiple species can determine exactly which fish patients may be allergic to, according to a study published in The Journal of Allergy and Clinical Immunology: In Practice.
This testing can help eliminate unnecessary food challenges and enable patients to eat fish they otherwise would have avoided, the researchers wrote.
“We have been actively working toward improvement of diagnostic approaches of fish allergy because different patients are allergic to different fish species and may hence safely consume other fish species,” authors Tanja Kalic, PhD, a postdoctoral researcher in the department of dermatology at University Hospital St. Pölten, Karl Landsteiner University of Health Sciences in St. Pölten, Austria, and Heimo Breiteneder, PhD, a professor of pathophysiology and allergy research in the division of medical biotechnology, department of pathophysiology and allergy research at the Center for Pathophysiology, Infectiology and Immunology of Medical University of Vienna, told Healio in a statement.
Patients allergic to one fish type are usually advised to avoid all fish, leading to dietary restrictions and a negative impact on quality of life, they added.
“The reason for adhering to this procedure is the lack of appropriate diagnostic assays,” Kalic and Breiteneder said. “While the ultimate confirmation of tolerance to a specific fish species must be performed by a food challenge, clinicians are not able to do food challenges with many different fish species. Our research aimed to develop a diagnostic assay that would allow to narrow down the number of required food challenges.”
The study’s design, results
The cohort comprised 263 patients (median age, 12 years; range, 1-65; 160 males) from Austria, China, Denmark, Luxembourg, Norway and Spain with a documented clinical history of fish allergy and confirmed sensitization to fish.
The researchers used a research version of the ALEX2 multiplex assay (Macro Array Diagnostics) to test specific IgE to parvalbumins from nine bony fish species and one cartilaginous species, the thornback ray. They also quantified raw and heated extracts from seven species.
Results showed that ray alpha-parvalbumin and sole and cod beta-parvalbumins had the lowest median sIgE, whereas mackerel and tuna parvalbumin had the highest. Specifically, the IgE of only 22% of the cohort recognized ray parvalbumin, indicating its low allergenicity, whereas sensitization reached 92% for tuna.
Twenty-five percent of patients were negative to sole parvalbumin (highest in Luxembourg, 41%), and 19% were negative to cod parvalbumin (highest in China, 38%).
“The most commonly used fish allergen in diagnosis is cod parvalbumin, Gad m 1. In our 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,” Kalic and Breiteneder said.
Researchers observed weak correlations between pairs of parvalbumins from ray and the bony fish (Spearman’s correlation coefficient, 0.42), although there were strong and statistically significant correlations between beta-parvalbumin pair values. In fact, the researchers found that a positive test for any beta-parvalbumin resulted in a greater than 80% probability of positivity to other beta-parvalbumins.
The beta-parvalbumins for tuna, mackerel and carp best predicted highly probable negative tests for other beta-parvalbumins, the researchers found, adding that this finding may help inform the design of species panels for tolerance-confirming food challenges.
Analyzing raw, heated extracts
When data for parvalbumin and raw and heated extracts are combined, the researchers wrote, clinicians can predict possible tolerance to specific species when tolerance of other species is known.
Raw and heated extracts can confirm IgE for other fish allergens before beginning food challenges as well, the researchers wrote, finding that 45 patients (17%) tested negative to parvalbumins but positive to fish extracts.
Among 44 patients with higher IgE values to extracts than to parvalbumin from one or more species, up to seven patients per species had no IgE for the respective IgE but were positive for raw and heated extracts. Parvalbumin-sIgE quantification alone for these patients could lead to false-negative diagnoses for some species, the researchers cautioned. “We recommend starting with a multiplex IgE assay that includes purified parvalbumins and whole extracts from various fish species, bony and cartilaginous,” Kalic and Breiteneder said.
Researchers then used the total data that identified patients negative to IgE tests to parvalbumin, raw extracts and heat extracts.
“Between 60% (Spain) and 90% (Luxembourg) of the patients tested negative to thornback ray,” Kalic and Breiteneder said.
Also, they continued, up to 21% of patients, depending on their country of origin, may tolerate specific species of bony fish.
Researchers 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.
ALEX2 is the only currently available multiplex test that includes parvalbumins and extracts from several bony fish and one cartilaginous fish, the researchers wrote. Doctors can begin testing to improve the quality of life of patients by reducing their need to practice broader diet avoidance, they added
“If a patient tests negative on one or several fish species, then a focused food challenge can be performed,” Kalic and Breiteneder said.
For more information:
Heimo Breiteneder, PhD, can be reached at heimo.breiteneder@meduniwien.ac.at.
Tanja Kalic, PhD, can be reached at tanja.kalic@meduniwien.ac.at.
Perspective
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These results are significant, as there has not been an abundance of fish allergy data to guide allergists in recommendations to patients. The wide variety of fish species but limited capability to test for an allergy to a specific species has left allergists in the difficult spot of having to give a blanket recommendation for patients to avoid all finned fish. This may unnecessarily restrict some fish from patients’ diets, which is why it is important to distinguish what is safe from what is potentially dangerous.
This testing may be beneficial in giving allergists an avenue to more specifically test a variety of fish and reduce the number of oral food challenges that patients need. As the study states, food challenges pose a risk and can be laborious for clinicians. Minimizing the number of challenges that allergists have to perform while safely maximizing a patient's diet would be valuable.
This testing is more extensive than what has been clinically available. But before doctors can begin using this process in their own practice, more data showing reproducible results and expansion to more fish species would be necessary. Further clinical trials and validation of these tests would be the next steps in this research.
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