Fact checked byKristen Dowd

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August 18, 2023
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Alpha-tryptase may indicate potential for severe food allergy reactions

Fact checked byKristen Dowd
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Key takeaways:

  • Patients with alpha tryptase had more anaphylaxis than patients who only had B-tryptase.
  • 65% of patients with alpha-tryptase and 17% of patients with only B-tryptase had a severe reaction.

Patients with alpha-tryptase experienced more anaphylaxis and other severe reactions to food compared with patients who did not have alpha-tryptase, according to a study published in The Journal of Allergy & Clinical Immunology.

Genotyping for alpha-tryptase may help clinicians predict the severity of food allergy reactions, Abigail T. Lang, MD, MSci, attending physician in the department of allergy and immunology at Ann and Robert H. Lurie Children’s Hospital of Chicago, and colleagues wrote.

Peanuts in a bowl
10% of the patients who had a severe reaction during peanut OFCs had hereditary alpha-tryptase, but none of the patients who experienced mild reactions had it. Image: Adobe Stock

“As clinicians, we are often asked by patients and families if a food allergy is mild or severe. Worries about reaction severity often significantly impact quality of life for patients with food allergies,” Lang told Healio.

“Currently available clinical tests do not accurately distinguish between patients at risk for severe and potentially life-threatening allergic reactions to foods vs. more mild reactions,” she continued.

Abigail T. Lang

The study involved 82 patients (median age, 9 years) with food allergy from a National Institute of Allergy and Infectious Diseases cohort and 37 patients (median age, 3 years) who had oral food challenges for peanut allergy at Ann and Robert H. Lurie Children’s Hospital of Chicago.

Most of the participants were male and white and had at least one other comorbid allergic condition.

The patients in the NIAID cohort included 61 with a history of food allergy anaphylaxis. The Lurie cohort had 21 patients with severe reactions, defined by symptoms of anaphylaxis or documentation of epinephrine, and 16 with mild reactions, mostly urticaria, angioedema, rash or erythema.

“Our study investigated the use of a genetic biomarker for quantifying the presence of alpha-tryptase (genotyping of the TPSAB1 gene) to predict food allergy severity,” Lang said.

Since human genetic material or DNA does not change, Lang said, this test can be useful and obtained at the time of diagnosis since alpha-tryptase can be gathered via blood draw, saliva or buccal swabs, making it relatively easy to collect samples.

“This test is already commercially available and does not require major special processing or procedures to ensure sample stability such as other research tests like the basophil activation test,” she said.

Three patients (3.7%) in the NIAID cohort and two patients in the Lurie cohort (5%) had hereditary alpha tryptasemia (H-alpha-T). Most patients in both groups had at least one alpha-tryptase encoding gene copy.

Across both cohorts, 31 patients (26%) were genotyped as BB:BB, compared with 32% across the general population. AlphaB:BB was the most common tryptase in both cohorts, and it is the most common tryptase in the general population as well.

The three patients in the NIAID cohort with H-alpha-T had a history of anaphylaxis to food. Also, compared with patients who only had B-tryptase, patients with alpha-tryptase were significantly more likely to have a history of anaphylaxis to food (P = .026).

The patients with alpha-tryptase had Severity Grading Scale for Acute Reactions (SGSAR) scores that trended higher than the patients who did not have alpha-tryptase as well.

Two of the 21 patients with severe reactions (10%) in the Lurie cohort had H-alpha-T, but none of the 16 patients with mild reactions had it. Also, one of the six patients (17%) who only had B-tryptase and 20 of the 31 patients (65%) with alpha-tryptase had a severe reaction during OFCs.

The patients with alpha-tryptase had higher total SGSAR scores than the patients who had isoforms with no alpha-tryptase (BB:BB) during OFCs as well (P = .003). The correlations between alpha-tryptase copy number and higher total SGSAR scores (P = .008) and Bock/PRACTALL symptom scores (P= .003) were significant too, the researchers added.

The researchers did not find any significant differences between the patients who did and did not have H-alpha-T in asthma, eczema or allergic rhinitis prevalence in either cohort, but the patients with H-alpha-T did trend toward increased rates of drug allergy and Hymenoptera venom allergy.

The patients with H-alpha-T in the NIAID cohort trended toward increased total numbers of allergic reactions and reactions during OFC, the researchers continued. In fact, the researchers said, 10% of patients with severe reactions to peanut OFC and 5.7% of the general population had H-alpha-T.

However, the researchers did not find any significant differences in the prevalence of multiple food allergies or peanut allergy or in histories of epinephrine autoinjector use, eosinophilic gastrointestinal disease or urticaria.

Before the OFC, the researchers said, most of the patients in the Lurie cohort had at least one result from peanut skin prick testing, peanut-specific IgE or peanut component testing but there were no significant differences between the groups when the testing results were categorized by alpha-tryptase isoform number.

“We found that the presence of any alpha-tryptase was associated with increased risk of anaphylaxis or severe reaction to food compared to subjects without any alpha-tryptase,” Lang said.

“Additionally, there was no difference in the results of peanut skin prick test or specific IgE to peanut or components when stratified by alpha-tryptase isoform, which suggests that tryptase composition is an independent predictor of food allergy reaction severity,” she said.

“These results are significant because we are the first group to investigate tryptase genotype as a potential biomarker in food allergy,” Lang said.

Based on these findings, the researchers concluded that there were associations between the presence of germline alpha-tryptase encoding sequences and more severe allergic reactions to foods as well as between the presence of alpha-tryptase and increased prevalence of anaphylaxis and severe reactions to food.

Tryptase genotyping and alpha-tryptase-encoding copy numbers may be useful biomarkers in determining risks for severe reactions among patients with food allergy, the researchers wrote, although they cautioned that additional data from larger studies are needed to determine whether this approach would be effective.

“While our results are preliminary findings, tryptase genotype as a biomarker in food allergy seems promising,” Lang said. “In the future, physicians may be better able to use tryptase genotyping to better counsel patients and families about their risk of severe reactions.”

Lang and her colleagues are now applying for additional grant funds to expand upon their initial pilot project.

“We intend to include patients with allergies to foods other than peanut and will enroll a larger prospective cohort presenting to the emergency department for treatment of food-induced anaphylaxis,” she said.

“We also are planning to work with translational scientists to further elucidate the mechanism by which the presence of alpha-tryptase and tryptase heterotetramers contribute to food allergy severity,” she said.