Researchers make a major advancement in food allergy diagnosis

Peanut allergies are among the most severe and prevalent food allergies, particularly affecting children. These allergies can lead to life-threatening reactions, imposing a heavy burden on individuals, families, healthcare systems, and the food industry. Accurate and accessible diagnostic methods are essential for managing this condition effectively.

Traditional tests like the skin prick test (SPT), specific IgE (sIgE) measurements, and oral food challenges (OFC) often fall short of providing precise results. However, a novel laboratory-based mast cell activation test (MAT) using genetically engineered Hoxb8 mast cells has demonstrated superior diagnostic accuracy, offering new hope for allergy diagnostics.

The gold standard for diagnosing peanut allergies has long been the OFC, where patients consume small amounts of peanut under medical supervision. While highly accurate, this test is resource-intensive, carries health risks, and can provoke anxiety. Alternative diagnostic methods, such as SPT and sIgE measurements, are less invasive but have limitations. They frequently produce false positives, leading to overdiagnosis and unnecessary dietary restrictions.

SPT involves introducing allergens to the skin and measuring the resulting wheal size, while sIgE tests quantify allergen-specific antibodies in the blood. Although these tests offer high sensitivity, they often lack specificity.

For instance, sIgE levels may not indicate the functional activity of antibodies or their potential to trigger allergic reactions. Additionally, these tests do not account for protective factors, such as allergen-specific IgG. This makes it challenging to distinguish between sensitization (a positive test result without symptoms) and true allergies.

Functional cell-based tests like the basophil activation test (BAT) have emerged as promising alternatives. BAT measures basophil activation in response to allergens but requires fresh blood samples processed within 24 hours, limiting its practicality. Furthermore, some individuals exhibit nonresponsive basophils, reducing the test’s reliability. These challenges have spurred interest in developing more robust and scalable diagnostic methods.

Researchers at the University of Bern have developed a groundbreaking MAT leveraging genetically engineered Hoxb8 mast cells. These cells are cultured in the laboratory and designed to stably express human high-affinity IgE receptors.

This innovation, published in the journal, Allergy, enables the cells to be sensitized with patient serum, eliminating the need for fresh blood samples. By simulating allergic reactions in a controlled environment, the test provides functional insights into IgE-mediated allergies.

In the Hoxb8 MAT, mast cells are exposed to serum samples from patients suspected of having peanut allergies. The cells are then stimulated with peanut extract, and their activation is quantified using a flow cytometric marker, CD107a. This approach evaluates the allergenic potential of IgE antibodies, offering a functional assessment absent in traditional tests.

The process begins with the preparation of serum samples, which are filtered to ensure consistent results. Mast cells are sensitized with the serum overnight, allowing them to bind IgE antibodies. The following day, the cells are stimulated with varying concentrations of peanut extract, and their response is measured. The test’s ability to detect allergenic activity even in low IgE concentrations highlights its sensitivity and precision.

A clinical study conducted in collaboration with the Hospital for Sick Kids in Toronto assessed the Hoxb8 MAT’s efficacy. The study analyzed 112 serum samples from children and adolescents, including 80 confirmed peanut-allergic individuals and 32 nonallergic controls. The samples were stored at -80°C, ensuring stability before testing. Researchers compared the Hoxb8 MAT results with traditional diagnostic methods, including SPT, sIgE measurements, and BAT.

The findings revealed that the Hoxb8 MAT exhibited exceptional diagnostic accuracy. Using a cutoff of ≤5.2% CD107a-positive cells, the test achieved a sensitivity of 93% and specificity of 96% at allergen concentrations of 100 ng/mL or higher. These results surpassed the diagnostic accuracy of both SPT and sIgE tests. Notably, the test accurately classified nonresponsive basophils and peanut-tolerant individuals, addressing a significant limitation of BAT.

The study demonstrated the dose-dependent activation of mast cells in peanut-allergic patients, while nonallergic controls showed minimal activation. Even individuals with low levels of allergen-specific IgE were correctly identified as allergic. This functional assessment reduces the likelihood of false positives, offering a more reliable diagnostic tool.

Notably, the Hoxb8 MAT’s robustness was evident in its ability to process all samples within two days, showcasing its efficiency. Additionally, the test’s reliance on stored serum samples simplifies logistics, enabling retrospective analyses and broader accessibility.

"The new test is functional and incorporates many parameters important for triggering allergies," explained Professor Thomas Kaufmann, one of the study’s principal investigators. “It offers a more comprehensive understanding of the patient’s allergic response.”

The Hoxb8 MAT represents a significant advancement in allergy diagnostics. Unlike traditional tests, it accounts for the functional properties of IgE antibodies and integrates key parameters influencing allergic reactions. The test’s reliance on stable serum samples simplifies logistics, making it accessible for prospective and retrospective analyses. This approach also minimizes the variability associated with donor-dependent factors.

In addition to its diagnostic accuracy, the Hoxb8 MAT can be applied to other allergies beyond peanuts, potentially transforming allergy diagnostics. For example, the method can be tailored to evaluate responses to milk, eggs, and tree nuts, offering a versatile platform for allergen testing. Such applications could alleviate the need for invasive tests and enhance patient care.

Researchers have also explored the potential for using the Hoxb8 MAT in cases where traditional tests are inconclusive. For instance, patients with ambiguous results from SPT or sIgE measurements could benefit from the MAT’s detailed functional insights. Furthermore, the test’s compatibility with biobanked samples opens opportunities for longitudinal studies, tracking allergic responses over time.

“What has been shown in this study on the diagnosis of peanut allergies can also be applied to other allergies in a simple way,” said Professor Alexander Eggel. “This technology is a perfect example of how basic research can be brought into clinical practice, ultimately simplifying life for patients and physicians.”

The University of Bern has patented the Hoxb8 MAT technology, and the researchers have founded ATANIS Biotech AG to commercialize the test. The company aims to certify the MAT and market it globally, revolutionizing allergy diagnostics. With over 20 employees, ATANIS is poised to transform clinical practices and improve the quality of life for allergy sufferers worldwide.

The development of the Hoxb8 MAT underscores the importance of innovation in addressing global health challenges. Food allergies affect up to 10% of the population in some regions, primarily young children. The economic and emotional toll of managing these allergies is substantial. By offering a safer, more accurate diagnostic method, the Hoxb8 MAT has the potential to reduce unnecessary dietary restrictions and improve patient outcomes.

Moreover, the technology aligns with ongoing efforts to personalize medicine. By tailoring diagnostic tools to individual immune responses, clinicians can develop targeted management strategies, minimizing the risk of adverse reactions. This approach not only enhances patient care but also reduces healthcare costs associated with misdiagnosis and over-treatment.

As the Hoxb8 MAT gains traction, it may inspire further advancements in allergy research. The test’s modular design allows for continuous refinement, incorporating new biomarkers and allergens. This adaptability ensures its relevance in an ever-evolving field, addressing emerging allergens and changing environmental factors.

The Hoxb8 MAT represents a paradigm shift in allergy diagnostics. By combining scientific innovation with practical application, it bridges the gap between laboratory research and clinical practice.

As this technology becomes widely available, it promises to alleviate the burden of food allergies, offering a brighter future for patients and their families.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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