A novel human mast cell activation test for peanut allergy

Santos, Alexandra; Couto-Francisco, Natália C.; Bécares, Natalia; Kwok, Matthew; Bahnson, Henry T.; Lack, Gideon

doi:10.1016/j.jaci.2018.03.011

Cited by 89 publications

(81 citation statements)

References 9 publications

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“…BAT did not show a significant advantage . In addition, promising results on the usage of passive sensitization strategies using the mast cell lines or mast cell precursors have been reported. Larger, real‐life studies are demanded to confirm that passive sensitization strategies, which are technically more demanding but have the advantage of using serum instead of fresh blood, are as reliable as the conventional approach.…”

Section: Introductionmentioning

confidence: 94%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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The achievement of long-lasting, safe treatments for food allergy is dependent on the understanding of the immunological basis of food allergy. Accurate diagnosis is essential for management. In recent years, data from oral food challenges have revealed that routine allergy testing is poor at predicting clinical allergy for tree nuts, almonds in particular. More advanced antigen-based tests including component-resolved diagnostics and epitope reactivity may lead to more accurate diagnosis and selection of therapeutic intervention. Additional diagnostic accuracy may come from cellular tests such as the basophil activation test or mast cell approaches. In the context of clinical trials, cellular tests have revealed specific T-cell and B-cell populations that are more abundant in food-allergic individuals with distinct mechanistic features.Awareness of clinical markers, such as the ability to eat baked forms of milk and egg, continues to inform the understanding of natural tolerance development.Mouse models have allowed for investigation into multiple mechanisms of food allergy including modification of epithelial metabolism, and the induction of regulatory cell subsets and the microbiome. Increasing numbers of children who underwent food immunotherapy enlarged the body of evidence on mechanisms and predictors of treatment success. Experimental immunological markers in conjunction with clinical determinants such as lower age and lower initial specific IgE appear to be of benefit.More research on the optimal dose, preparation, and route of application integrating a high-level safety and efficacy is demanded. Alternatively, biologics blocking TSLP, IL-33, IL-4 and IL-13, or IgE may help to achieve that. K E Y W O R D Sallergy treatment, biologics, food allergy, immune tolerance, immunotherapy | 2357 EIWEGGER Et al.

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Section: Introductionmentioning

confidence: 94%

Recent developments and highlights in food allergy

Eiwegger

Hung

Diego

et al. 2019

Allergy

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“…In the MAT, which includes a washing step between sensitization with plasma and stimulation with allergen, the proportion of activated mast cells in response to peanut was similar before and after treatment (Fig 2, A), indicating that the functionality of IgE did not change after POIT, as opposed to what we have previously observed using the same assay to test samples of patients with peanut allergy and peanut-sensitized but tolerant patients. 4 The mast cell response to polyclonal anti-IgE was greater after POIT (Fig 2, B), suggesting that the IgE-mediated pathway was primed after continued allergen exposure, possibly because of the increase in IgE characteristics such as IgE affinity, given that the cells were the same but sensitized with different plasma in pre-and post-POIT conditions.…”

Section: Peanut Oral Immunotherapy Induces Blocking Antibodies But Domentioning

confidence: 94%

“…IgG 4 /IgE ratios were determined after conversion of kilounits per liter (IgE) and milligrams per liter (IgG 4 ) to nanograms per milliliter, as previously described. 2 For mast cell assays, 2,4 LAD2 cells were placed in culture with rIL-4 for 5 days before overnight sensitization with patients' plasma from before or after POIT. Sensitized cells were stimulated with peanut extract, anti-IgE, ionomycin, or 0.04% BSA RPMI alone for 30 minutes at 378C and stained with the viability dye eFluor 450 and CD107b-fluorescein isothiocyanate (eBioscience, San Diego, Calif), CD203c-phycoerythrin, CD107a-peridinin-chlorophyll-protein complex-Cy5.5, CD63allophycocyanin, and IgE-phycoerythrin-Cy7 (BioLegend, San Diego, Calif) and analyzed by using flow cytometry.…”

Section: Peanut Oral Immunotherapy Induces Blocking Antibodies But Domentioning

confidence: 99%

Peanut oral immunotherapy induces blocking antibodies but does not change the functional characteristics of peanut-specific IgE

Santos

James

Kwok

et al. 2020

Journal of Allergy and Clinical Immunology

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“…This proposed approach reduced the number of OFC by 67% in a previous study of peanut allergy 40 . To circumvent the major limitations of BAT, which are the need for fresh blood and the 10-15% non-responders, the mast cell activation test (MAT) may be used to complement the BAT 97 .…”

Section: Clinical Validation Of the Basophil Activation Testmentioning

confidence: 99%

Basophil activation test: mechanisms and considerations for use in clinical trials and clinical practice

Santos

Alpan

Hoffmann

2020

Preprint

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The basophil activation test (BAT) is a functional assay that measures the degree of degranulation following stimulation with allergen or controls by flow cytometry and is directly correlated with histamine release. From the bell-shaped curve resulting from BAT in allergic patients, basophil reactivity (given by %CD63+ basophils) and basophil sensitivity (given by EC50 or similar) are the main outcomes of the test. BAT takes into account all characteristics of IgE and allergen and thus can be more specific than sensitization tests in the diagnosis of allergic disease. BAT reduces the need for in vivo procedures, such as intradermal tests and allergen challenges, which can cause allergic reactions of unpredictable severity. As it closely reflects the patients' phenotype, it can potentially be used to monitor the natural resolution of food allergies and to predict and monitor clinical response to immunomodulatory treatments, such as allergen-specific immunotherapy and biologicals. Clinical application of BAT requires analytical validation, clinical validation, standardization of procedures and quality assurance to ensure reproducibility and reliability of results. Currently, efforts are ongoing to establish a platform that could be used by laboratories in Europe and in the USA for certification.

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A novel human mast cell activation test for peanut allergy

Cited by 89 publications

References 9 publications

Recent developments and highlights in food allergy

Recent developments and highlights in food allergy

Peanut oral immunotherapy induces blocking antibodies but does not change the functional characteristics of peanut-specific IgE

Basophil activation test: mechanisms and considerations for use in clinical trials and clinical practice

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