LAD2 mast cell activation test associates with the reaction severity and diagnoses BAT nonresponders in Hymenoptera venom allergy.

BACKGROUND AND OBJECTIVE: The usefulness of the mast cell activation test (MAT) in diagnosing patients with uninterpretable basophil activation test (BAT) caused by nonresponding basophils has not yet been addressed. It should be further evaluated if the results of MAT are associated with the severity of the allergic reaction. METHODS: We recruited 39 Hymenoptera venom allergic (HVA) patients, 22 non-sensitized controls, and 37 BAT nonresponding HVA patients. Specific IgE levels for honey bee venom (HBV), yellow jacket venom (YJV) and total IgEs were quantified using the Immulite system. BAT and MAT with LAD2 cells in response to HBV and YJV were performed. RESULTS: We first optimized the susceptibility of LAD2 cells to IgE-mediated degranulation in HVA and showed that prestimulation with IL-33 and IL-6 significantly increased the LAD2 cells´ responsiveness to allergen stimulation (P<0.01). LAD2 MAT results correlated with BAT results, and patients with severe sting reactions (Mueller grades IV or III) had a median 2-fold higher LAD2 MAT than the patients with nonsevere sting reactions (Mueller grades II, I or LLR) (P<0.05). Further, LAD2 MAT provided conclusive results in 54.1% (20 of 37) of HVA patients with nonresponding basophils in the BAT. CONCLUSION: The LAD2 MAT represents a new diagnostic tool for HVA patients with nonresponding basophils. Further, LAD2 MAT can identify patients at risk of severe sting reactions and thus can help guide recommendations for venom immunotherapy and improve the management of patients with HVA.