Systematic characterization of basophil anergy

Puan, Kia Joo; Andiappan, Anand Kumar; Lee, Bernett; Kumar, Dilip; Lai, Tuck Siong; Yeo, Giminna; Bercin, Derya; Starke, Mireille; Haase, Doreen; Lum, Josephine; Chew, Fook Tim; Connolly, John E.; Wong, Siew Cheng; Zolezzi, Francesca; Poidinger, Michael; Wang, De Yun; Rötzschke, Olaf

doi:10.1111/all.12952

Cited by 35 publications

(53 citation statements)

References 41 publications

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“…Future experiments might clarify whether addressing MRGPRX2 is useful for diagnostic purposes in allergic and pseudoallergic reactions like CD63 or CD203c . In addition, it might be interesting to investigate whether anergic nonresponder basophils to anti‐FcεRI respond to MRGPRX2 engagement.…”

Section: Discussionmentioning

confidence: 99%

The pseudoallergen receptor MRGPRX2 on peripheral blood basophils and eosinophils: Expression and function

Wedi

Gehring

Kapp

2020

Allergy

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Background Mas‐related G protein‐coupled receptor X2 (MRGPRX2) is regarded as a mast cell‐specific receptor mediating non–IgE‐dependent activation. We aimed to investigate whether human basophils and eosinophils express functional MRGPRX2. Methods Flow cytometry, immunocytochemistry, immunofluorescence, Western blot, and RT‐PCR were performed in highly purified peripheral blood basophils and eosinophils of atopic and nonatopic donors. To assess functional activity, fluorescent avidin‐based degranulation assay, calcium mobilization, cytokine production in supernatants, assessment of viability/apoptosis, and tricolor granulocyte activation test were used. Results MRGPRX2 was significantly expressed by basophils and eosinophils but not neutrophils. Functional capacity was shown by anti‐MRGPRX2 mAb‐induced calcium influx and concentration‐dependent induction of degranulation. Sequential stimulation in the calcium mobilization assay gave no evidence for desensitization or receptor internalization. Anti‐MRGPRX2 mAb significantly promoted survival. Inhibition of apoptosis could be due to released IL‐3, IL‐5, and GM‐CSF found in supernatants. Short‐term incubation with IL‐3 dose‐dependently upregulated MRGPRX2 expression in both, stimulation for 24 hours with anti‐IgE, C5a, fMLP, and IL‐3 in basophils and by IL‐3, IL‐5, and IL‐33 in eosinophils. Among known mast cell MRGPRX2 agonists ciprofloxacin but not PMX‐53 was functional on basophils and eosinophils. In basophils of allergic subjects, tricolor granulocyte activation test using grass pollen demonstrated MRGPRX2 upregulation associated with degranulation and CD63 expression. Conclusion Unraveling the regulation and signaling mechanisms of MRGPRX2 on basophils and eosinophils might enable the development of new therapeutic strategies to prevent or inhibit allergic and nonallergic hypersensitivity. Moreover, addressing MRGPRX2 might have potential for diagnostic purposes in (drug) hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

The pseudoallergen receptor MRGPRX2 on peripheral blood basophils and eosinophils: Expression and function

Wedi

Gehring

Kapp

2020

Allergy

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“…First, it provides a reasonable explanation for the high variability in maximum IgE-mediated histamine release from basophils (in vitro). [2][3][4] Second, it appears that starting levels of SYK expression in basophils are predictive of the efficacy of omalizumab treatment in patients with asthma or peanut allergy. 5,6 The implication of the latter observation is that basophils play a significant role in expression of food allergy or asthma.…”

mentioning

confidence: 99%

Autoantibodies to IgE and FcεRI and the natural variability of spleen tyrosine kinase expression in basophils

MacGlashan

2019

Journal of Allergy and Clinical Immunology

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“…The nonresponder state has also been reversed experimentally in vitro by culturing basophils in the presence of IL-3 26 . In a large study performed in Singapore, basophil non-responsiveness was associated with lower amounts of basophil Syk, and an apparent reduction of the incidence of rhinitis; basophil non-responsiveness thus may be a final barrier of the immune system to prevent unwanted reactions against allergens 24 . As the amount of allergen-specific IgE increases, the amount of basophil Syk is transiently decreased by allergen exposure to limit the allergic response.…”

Section: The Importance Of Non-ige and Ige-mediated Controls And The mentioning

confidence: 98%

“…One cause of non-responsiveness is a low level of Syk phosphatase [21][22][23] , possibly in combination with elevated amounts of CD45 13 . The non-responder phase is transient; a patient may revert to a responsive state within months 24,25 . The nonresponder state has also been reversed experimentally in vitro by culturing basophils in the presence of IL-3 26 .…”

Section: The Importance Of Non-ige and Ige-mediated Controls And The mentioning

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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Systematic characterization of basophil anergy

Abstract: Basophil anergy thus seems to function as activation barrier to prevent unwanted reactions against minor allergens. It may therefore be relevant for diagnostic purposes or therapeutic interventions of allergic diseases.

Cited by 35 publications

References 41 publications

The pseudoallergen receptor MRGPRX2 on peripheral blood basophils and eosinophils: Expression and function

The pseudoallergen receptor MRGPRX2 on peripheral blood basophils and eosinophils: Expression and function

Autoantibodies to IgE and FcεRI and the natural variability of spleen tyrosine kinase expression in basophils

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

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