Zbären, Noemi; Brigger, Daniel; Bachmann, Daniel; Helbling, Arthur; Jörg, Lukas; Horn, Michael; Schmid, Johannes M; Hoffmann, Hans Jürgen; Kinet, Jean-Pierre; Kaufmann, Thomas; Eggel, Alexander (2022). A novel functional mast cell assay for the detection of allergies. The Journal of allergy and clinical immunology, 149(3), 1018-1030.e11. Elsevier 10.1016/j.jaci.2021.08.006
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BACKGROUND
Clinical management of allergic diseases has been hampered by the lack of safe and convenient tests to reliably identify culprit allergens and to closely follow changes in disease activity over time. Since allergy diagnosis is a complex and laborious multistep procedure, there is an urgent need for simpler but still functionally accurate ex vivo assays allowing objective diagnosis, substantiating treatment choices and quantifying therapeutic responses.
OBJECTIVE
In this study, we sought to develop a novel functional cell-based assay that relies on passive sensitization of allergic effector cells with patient serum circumventing current limitations in allergy diagnosis.
METHODS
We genetically engineered a conditional Hoxb8-immortalized progenitor line from the bone-marrow of mice that are transgenic for the human high-affinity IgE receptor (FcεRIα). These cells can be reproducibly differentiated into mature Hoxb8 mast cells (Hoxb8 MCs) within in 5 days of culture in virtually unlimited numbers.
RESULTS
We demonstrate that the established Hoxb8 MC assay can be used to accurately measure total IgE levels, identify culprit allergens, longitudinally monitor allergen-specific immunotherapy (AIT) and potentially to determine the timepoint of tolerance induction upon AIT in allergic patients. To facilitate the analysis of large testing volumes, we demonstrate a proof-of-concept for a high-throughput screening application based on fluorescent cell barcoding using the engineered Hoxb8 MCs.
CONCLUSION
Our results indicate that this novel mast cell assay could represent a valuable tool to support clinicians in the identification of IgE-mediated allergies and in the quantification of treatment efficacy as well as duration of therapeutic response.
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