Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children

Santos, Alexandra; Douiri, Abdel; Bécares, Natalia; Wu, Shijuan; Stephens, Alick; Radulović, Suzana; Chan, Susan; A, Fox; Toit, George Du; Turcanu, Victor; Lack, Gideon

doi:10.1016/j.jaci.2014.04.039

Cited by 244 publications

(372 citation statements)

References 33 publications

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“…Further repertoire analysis of CD4+ T cells during IT may reveal the preferential deletion or reprogramming of T cells based on factors like functional avidity or structural TCR avidity. Additionally, several IT studies, particularly for allergy, have identified changes in antigen-specific IgE and IgG responses, regulatory B cells, and basophils associated with tolerance induction (13,17,39,46,51).…”

Section: Discussionmentioning

confidence: 99%

Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets

Ryan

Hovde

Glanville

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

124

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Allergen immunotherapy can desensitize even subjects with potentially lethal allergies, but the changes induced in T cells that underpin successful immunotherapy remain poorly understood. In a cohort of peanut-allergic participants, we used allergen-specific T-cell sorting and single-cell gene expression to trace the transcriptional "roadmap" of individual CD4+ T cells throughout immunotherapy. We found that successful immunotherapy induces allergen-specific CD4+ T cells to expand and shift toward an "anergic" Th2 T-cell phenotype largely absent in both pretreatment participants and healthy controls. These findings show that sustained success, even after immunotherapy is withdrawn, is associated with the induction, expansion, and maintenance of immunotherapy-specific memory and naive T-cell phenotypes as early as 3 mo into immunotherapy. These results suggest an approach for immune monitoring participants undergoing immunotherapy to predict the success of future treatment and could have implications for immunotherapy targets in other diseases like cancer, autoimmune disease, and transplantation.is a process in which small amounts of allergen are given over time to the allergic individual until they can safely tolerate high amounts of allergen with no signs of clinical symptoms (1-9). In the regimen of oral IT for peanut-allergic patients (identified by an allergic reaction during a standardized blinded food challenge to peanut), small amounts of peanut flour protein are ingested and escalated to a servings-worth of peanut protein (4 g of peanut protein) over a period of 2-3 y (6-7). Most patients require continuous frequent (e.g., daily) exposure to such therapy for beneficial clinical outcomes. Mechanistic studies of oral IT to food allergens, although limited to date, show that plasma markers such as IgE and IgG4 immunoglobulins, skin test markers, component testing, and basophil activation tests are only weakly predictive of long-term clinical success (10-16). T cells are critical upstream regulators of allergic sensitization that are required to help B cells to synthesize IgE/IgG4 immunoglobulins, which then can activate or inhibit basophils and mast cells (10-17). Moreover, successful IT is associated with the development of regulatory T cells (Tregs) that are thought to dampen allergic reactivity to offending allergens (7). We therefore focused on finding T-cell markers of immune tolerance that could be detected early in the peripheral blood during IT. CD4+ T cells can be relatively long-lived (compared with plasma proteins and basophils) and changes detected early in populations of T cells could perhaps predict longer-lasting successful IT. For example, in one of the first studies in peanut allergen IT to withdraw therapy for more than 10 wk, we previously showed that despite negative skin tests to peanut, and high IgG4/low specific IgE levels to peanut, and decreased basophil reactivity to the allergen, some patients who withdrew from therapy for 3-6 mo were still reactive upon rechallenge with peanut (7...

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Section: Discussionmentioning

confidence: 99%

Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets

Ryan

Hovde

Glanville

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

126

124

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“…18,19 CD203c can be rapidly measured by flow cytometry and has been proposed as a diagnostic tool in atopic disease, including peanut, drug and wasp venom allergy. [20][21][22] It has been shown that basophils are primed and hyper-responsive to Af allergen stimulation in CF-ABPA. 18 In this current study, BAT to Af was employed to identify Af sensitization in a CF cohort and it was correlated with key CF clinical measurements.…”

Section: Abbreviationsmentioning

confidence: 99%

The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis

Mirković

Lavelle

Azim

et al. 2016

Journal of Allergy and Clinical Immunology

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“…By an in‐vitro dose‐response allergen stimulation of the basophils, their allergen threshold sensitivity, CD‐sens 16 can be accurately determined. Studies have shown that CD‐sens correlates significantly with bronchial allergen threshold sensitivity 9 , nasal allergen challenge 14, 18 , and oral food challenge 15, 19, 20 .…”

Section: Discussionmentioning

confidence: 99%

A clinical follow‐up of omalizumab in routine treatment of allergic asthma monitored by CD‐sens

Johansson

Lilja

Hallberg

et al. 2018

Immunity Inflam & Disease

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IntroductionOmalizumab has been available for treatment of allergic asthma for more than a decade and thus, its efficacy in routine treatment was of interest to evaluate. Basophil allergen threshold sensitivity (CD‐sens) has been shown to correlate with the bronchial allergen threshold sensitivity and can be used to objectively measure omalizumab treatment efficacy. We aimed to evaluate the effect of omalizumab treatment of allergic asthma by CD‐sens, as an objective marker of the IgE‐mediated inflammation, and related to SPT, spirometry, FeNO, Asthma Control Questionnaire (ACQ), and Global Evaluation of Treatment Effectiveness (GETE).MethodsThirty‐two patients were treated with omalizumab for 16 weeks. CD‐sens was used to define the response and related to clinical parameters. If CD‐sens was negative (<0.1) (CD‐sens low Group) the patient continued with the standard dose. If CD‐sens was ≥0.1 (CD‐sens high Group) a second 16 weeks period with 25–50% dosage increase was started and evaluated after a total of 32 weeks.ResultsNine of 32 patients became CD‐sens negative after treatment (CD‐sens start: 8.0; 16 weeks: <0.01) and regarded as successful. 15/23 were unsuccessful (CD‐sens start: 13; 16 weeks: 1.65) and the omalizumab dose was increased. CD‐sens decreased significantly (p < 0.05) and further 3/15 patients became CD‐sens negative (CD‐sens at 32 weeks: 0.5). There was a significantly smaller IgE‐ab fraction (IgE‐ab/IgE) in the CD‐sens low versus the CD‐sens high Group (p < 0.0001). A significant decrease in ACQ was seen in both groups after 16 weeks treatment (p = 0.05 and 0.01, respectively). No significant changes could be detected for the other clinical parameters.ConclusionBy the use of the objective laboratory method CD‐sens, which effectively measure the direct effect of omalizumab, that is, the IgE‐mediated part of the allergic asthma, in combination with clinical parameters it might be possible to more effectively monitor and treat IgE‐mediated allergic asthma.

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Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children

Cited by 244 publications

References 33 publications

Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets

Successful immunotherapy induces previously unidentified allergen-specific CD4+ T-cell subsets

The basophil surface marker CD203c identifies Aspergillus species sensitization in patients with cystic fibrosis

A clinical follow‐up of omalizumab in routine treatment of allergic asthma monitored by CD‐sens

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