A novel functional mast cell assay for the detection of allergies

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:149

Article

Zbaeren, Noemi^1,2  Brigger, Daniel^1,2  Bachmann, Daniel³  Helbling, Arthur⁴  Joerg, Lukas⁴  Horn, Michael P.⁵  Schmid, Johannes M.⁶  Hoffmann, Hans Juergen⁶  Kinet, Jean-Pierre⁷  Kaufmann, Thomas³  Eggel, Alexander^1,2 

[1] Univ Bern, Dept BioMed Res, Bern, Switzerland

[2] Univ Hosp Bern, Dept Rheumatol Immunol & Allergol, Bern, Switzerland

[3] Univ Bern, Inst Pharmacol, Bern, Switzerland

[4] Univ Hosp Bern, Inselspital, Dept Pneumol, Div Allergol & Clin Immunol, Bern, Switzerland

[5] Univ Hosp, Dept Clin Chem, Inselspital, Bern, Switzerland

[6] Aarhus Univ, Dept Clin Med, Dept Resp Dis & Allergy, Aarhus, Denmark

[7] Harvard Med Sch, Dept Pathol, Beth Israel Deaconess Med Ctr, Boston, MA USA

关键词: Allergies;    IgE;    diagnostic testing;    functional assay;    hu-man high-affinity IgE receptor;    mast cells;    immunotherapy monitoring;    homeobox B8;   

DOI  :  10.1016/j.jaci.2021.08.006

来源: Elsevier

【 摘 要 】

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 (Fc epsilon RIa). 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.

【 授权许可】

Free