A novel functional mast cell assay for the detection of allergies.

Autor: Zbären N; Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Rheumatology, Immunology and Allergology, University Hospital Bern, Bern, Switzerland., Brigger D; Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Rheumatology, Immunology and Allergology, University Hospital Bern, Bern, Switzerland., Bachmann D; Institute of Pharmacology, University of Bern, Bern, Switzerland., Helbling A; Division of Allergology and Clinical Immunology, Department of Pneumology, Inselspital, University Hospital Bern, Bern, Switzerland., Jörg L; Division of Allergology and Clinical Immunology, Department of Pneumology, Inselspital, University Hospital Bern, Bern, Switzerland., Horn MP; Department of Clinical Chemistry, Inselspital University Hospital, Bern, Switzerland., Schmid JM; Department of Respiratory Diseases and Allergy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Hoffmann HJ; Department of Respiratory Diseases and Allergy, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark., Kinet JP; Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Mass., Kaufmann T; Institute of Pharmacology, University of Bern, Bern, Switzerland. Electronic address: thomas.kaufmann@pki.unibe.ch., Eggel A; Department of BioMedical Research, University of Bern, Bern, Switzerland; Department of Rheumatology, Immunology and Allergology, University Hospital Bern, Bern, Switzerland. Electronic address: alexander.eggel@dbmr.unibe.ch.
Jazyk: angličtina
Zdroj: The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2022 Mar; Vol. 149 (3), pp. 1018-1030.e11. Date of Electronic Publication: 2021 Aug 18.
DOI: 10.1016/j.jaci.2021.08.006
Abstrakt: 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. Because 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 homeobox B8 (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 within 5 days of culture in virtually unlimited numbers.
Results: We demonstrate that the established Hoxb8 mast cell assay can be used to accurately measure total IgE levels, identify culprit allergens, longitudinally monitor allergen-specific immunotherapy, and potentially determine the time point of tolerance induction upon allergen-specific immunotherapy in patients with allergy. 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 mast cells.
Conclusions: 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.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: