A novel functional mast cell assay to diagnose allergies
Published: August 17, 2021
It is estimated that roughly one-third of the global population is suffering from allergic hypersensitivity disorders. For many affected patients allergies are associated with a marked reduction in physical and mental well-being and a significant loss in quality-of-life due to disease activity. To provide efficient and personalized treatment options, physicians depend on solid and reliable diagnostic tools. However, 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 simple, yet functionally accurate ex vivo assays allowing objective diagnosis, substantiating treatment choices and quantifying therapeutic responses.
In a recent article in The Journal of Allergy and Clinical Immunology (JACI), Zbären et al. describe the development of a novel functional cell-based assay that relies on passive sensitization of allergic effector cells with patient serum. This approach circumvents the risk of in vivo allergen challenges and the logistical limitations of ex vivo basophil activation testing. In their study, the authors engineered a conditionally immortalized mast cell progenitor line from the bone-marrow of mice that are transgenic for the high-affinity human IgE receptor. These progenitor cells were cultured for extended periods of time (several months) and their differentiation potential into fully mature mast cells expressing the human IgE receptor was investigated. In various proof-of-concept approaches the authors then assessed the functional characteristics of the newly generated mast cells and assessed their diagnostic utility.
First Zbären et al. established a protocol to reproducibly differentiate the progenitor line into mature mast cells within 5 days of culture in virtually unlimited numbers. They went on to demonstrate that these mast cells can be used to accurately measure total IgE levels in serum of patients, identify culprit allergens, longitudinally monitor allergen-specific immunotherapy (AIT), and potentially determine the timepoint of tolerance induction upon AIT. Importantly, the flow cytometry-based assay showed a remarkable signal-to-noise ratio with less than 1% background and over 95% maximal activation signal upon allergen challenge. To facilitate the analysis of large testing volumes, the authors further developed a high-throughput screening approach using fluorescent cell barcoding that allows simultaneous testing of multiple allergens or patient sera in an unprecedented rapid and standardized manner.
The results presented in this study suggest that the newly established mast cell assay provides comprehensive information on the allergic status of a patient and overcomes many challenges and limitations associated with current diagnostic tools. Thereby it could represent a valuable alternative to support clinicians in the identification of IgE-mediated allergies and in the quantification of treatment efficacy as well as duration of therapeutic response.
The Journal of Allergy and Clinical Immunology (JACI) is an official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.
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