Hoxb8 Mast Cell Activation Test Demonstrates Diagnostic Precision for Assessment of Peanut Allergy

The Hoxb8 mast cell activation test (MAT) demonstrated excellent diagnostic accuracy and precision, outperforming established diagnostic assays such as skin prick tests (SPTs) and specific immunoglobulin E (sIgE) in the diagnosis of peanut allergy while showing comparable efficacy to the basophil activation test (BAT), according to new research published in Allergy.^1,2

Accurate diagnosis of peanut allergy is essential for preventing harmful reactions. | Image Credit: © New Africa | stock.adobe.com

Diagnostic assays including SPT and sIgE are less elaborate in vivo tools to diagnose allergies compared with the gold standard of the oral food challenge (OFC) test. Access to these tests is limited, though, because they require significant resources, and the procedure is often associated with significant discomfort.¹

SPT and sIgE can be helpful to confirm a suspicion of allergies, but they are not sufficient to diagnose a food allergy on their own. Alternatively, cell-based allergy tests like the BAT have gained traction as promising methods to diagnose food allergies. These tests evaluate the activation of allergic effector cells to determine a diagnosis.^1,3

Previous research from the current investigator group has demonstrated the high accuracy of the BAT in the diagnosis of peanut and tree nut allergies. They found that the BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut allergy diagnosis.³

However, key limitations have made it difficult to broadly implement the BAT. Mainly, these include the variability between donor reactivity, being most problematic for so-called non-responders that have a lack of basophil activation. Logistical challenges surrounding the necessity of fresh blood samples also make broad implementation difficult.⁴

MATs have become a potential tool to circumvent such limitations. The test is based on patient serum, which eliminates the cumbersome need for fresh blood samples. Preliminary research has demonstrated that the new Hoxb8 MAT tool is a promising approach to provide standardized and robust results for various allergens. Therefore, in the current study, the investigators assessed the clinical utility of Hoxb8 MAT in diagnosing peanut allergies and compared it with outcomes from other diagnostic methods.¹

Hoxb8 MAT was found to successfully discriminate between peanut allergic and nonallergic children and adolescents. Area under the receiver operating characteristic curve (AUROC) at a 100 ng/mL peanut allergen dose was 0.97 for the Hoxb8 MAT, demonstrating consistent allergen dose-dependent increase of diagnostic accuracy. When directly comparing with BAT, a moderate but highly significant linear correlation was observed.¹

Importantly, Hoxb8 MAT demonstrated that it could accurately capture BAT non-responders. Seven patients that did not meet the qualifications for the previous BAT trial, 4 of which had clinically confirmed peanut allergies and 3 of which were nonallergic, were examined using the MAT test. All 4 samples from the peanut-allergic group showed dose-dependent activation, while no activation was observed from the nonallergic individuals.¹

"The cell-based test was easy to carry out and worked perfectly. All samples were measured within 2 days, which was very fast," Thomas Kauffman, an investigator on the study, said in a news release.²

Although the Hoxb8 MAT requires living cells and is therefore more laborious to perform, its functionality as an assay makes it more representative of the in vivo situation of a patient than an immunoassay that may assess the level—but not functionality—of specific antibodies. Part of Hoxb8’s effectiveness involves the integration of multiple qualitative and quantitative variables that play a role in the allergic response.¹

"An exceptionally high diagnostic accuracy of 95% could be calculated from these data," added Alexander Eggel, MD, the lead investigator of the trial.²

REFERENCES

1. Bachmeier-Zbären N, Celik A, van Brummelen R, et al. Clinical utility analysis of the Hoxb8 mast cell activation test for the diagnosis of peanut allergy. Allergy. Released online September 28, 2024. doi:10.1111/all.16341

2. University of Bern. New test improves diagnosis of allergies. ScienceDaily. News Release. Released October 15, 2024. Accessed November 15, 2024. https://www.sciencedaily.com/releases/2024/10/241015141449.htm

3. Duan L, Celik A, Hoang JA, et al. Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study. Allergy. 2021;76(6):1800-1812. doi:10.1111/all.14695

4. Kleine-Tebbe J, Erdmann S, Knol EF, et al. Diagnostic tests based on human basophils: Potentials, pitfalls and perspectives. Intl Archives of Allergy and Immunology. 2006;141(1):79-90. doi:10.1159/000094495