Predictive value of venom‐specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom

Müller, Ulrich; Helbling, Arthur; Bischof, Matthias

doi:10.1111/j.1398-9995.1989.tb04172.x

Cited by 151 publications

(95 citation statements)

References 21 publications

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“…2C). A decline of allergen-specific IgE and induction of allergen-specific IgG responses have been demonstrated in human subjects after IT (35,36). Accordingly, also levels of OVA-specific IgE were reduced in the present model in mice with OVA-IT, whereas levels of OVA-specific IgG1 were increased in comparison with sensitized and challenged animals (Fig.…”

Section: Resultsmentioning

confidence: 69%

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

Böhm

Maxeiner

Meyer-Martin

et al. 2015

The Journal of Immunology

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Human studies demonstrated that allergen-specific immunotherapy (IT) represents an effective treatment for allergic diseases. IT involves repeated administration of the sensitizing allergen, indicating a crucial contribution of T cells to its medicinal benefit. However, the underlying mechanisms of IT, especially in a chronic disease, are far from being definitive. In the current study, we sought to elucidate the suppressive mechanisms of IT in a mouse model of chronic allergic asthma. OVA-sensitized mice were challenged with OVA or PBS for 4 wk. After development of chronic airway inflammation, mice received OVA-specific IT or placebo alternately to airway challenge for 3 wk. To analyze the T cell–mediated mechanisms underlying IT in vivo, we elaborated the role of T-bet–expressing Th1 cells, T cell–derived IL-10, and Ag-specific thymic as well as peripherally induced Foxp3+ regulatory T (Treg) cells. IT ameliorated airway hyperresponsiveness and airway inflammation in a chronic asthma model. Of note, IT even resulted in a regression of structural changes in the airways following chronic inhaled allergen exposure. Concomitantly, IT induced Th1 cells, Foxp3+, and IL-10–producing Treg cells. Detailed analyses revealed that thymic Treg cells crucially contribute to the effectiveness of IT by promoting IL-10 production in Foxp3-negative T cells. Together with the peripherally induced Ag-specific Foxp3+ Treg cells, thymic Foxp3+ Treg cells orchestrate the curative mechanisms of IT. Taken together, we demonstrate that IT is effective in a chronic allergic disease and dependent on IL-10 and thymic as well as peripherally induced Ag-specific Treg cells.

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Section: Resultsmentioning

confidence: 69%

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

Böhm

Maxeiner

Meyer-Martin

et al. 2015

The Journal of Immunology

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“…However assays that detect only immunoreactive IgG4 are unlikely to predict clinical efficacy (Djurup et al, 1987;Muller et al, 1989;Ewan et al, 1993;Bodtger et al 2005). Therefore, measuring IgG4 concentration is not suitable for monitoring clinical efficacy of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

The IgE-facilitated allergen binding (FAB) assay: Validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses

Shamji

Wilcock

Wachholz

et al. 2006

Journal of Immunological Methods

137

129

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The IgE-Facilitated Allergen Binding (IgE-FAB) assay represents an in vitro model of facilitated allergen presentation. Allergen-IgE complexes are incubated with an EBV-transformed B-cell line and complexes bound to CD23 on the surface of cells are detected by flow cytometry. Addition of serum from patients who have received allergen-specific immunotherapy has been shown previously to inhibit allergen-IgE complex binding to CD23 on B cells.In this study, we describe the characterisation and analytical validation of the grass pollen-specific IgE-FAB assay according to guidelines from the International Conference on Harmonisation. We established the intra and inter -assay variability of IgE-FAB and have defined the detection limits of this assay. We have also demonstrated assay linearity and robustness. Using results from a randomised double-blind placebo controlled trial of grass pollen immunotherapy (n=33), we have defined the clinical sensitivity and specificity of the IgE-FAB assay using ROC curve analysis.In conclusion, the IgE-FAB assay is reproducible, robust, sensitive and specific method suitable as a tool for monitoring inhibitory antibody function from patients receiving allergen immunotherapy.

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“…The most prominent response to allergen IT treatment in allergic individuals is the induction of allergen-specific IgG1 and IgG4 responses, yet the relevance of the IT-induced IgG Ab response has remained controversial (1). Although some studies reported observations that indicate a contribution of blocking Abs to IT (41), several groups failed to show a correlation between the presence of neutralizing IgG Abs and improved clinical outcome (6,42). The allergen-specific IgG Abs might contribute to IT by blocking access of the allergen to IgE on mast cells or basophils or by preventing FcεRI-dependent mast cell activation by binding to FcgRIIB (reviewed in Ref.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice

Shirinbak

Taher

Maazi

et al. 2010

The Journal of Immunology

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Allergen-specific immunotherapy (IT) uniquely renders long-term relief from allergic symptoms and is associated with elevated serum levels of allergen-specific IgG and IgA. The allergen-specific IgG response induced by IT treatment was shown to be critical for suppression of the immediate phase of the allergic response in mice, and this suppression was partially dependent on signaling through FcγRIIB. To investigate the relevance of the allergen-specific IgG responses for suppression of the Th2-driven late-phase allergic response, we performed IT in a mouse model of allergic asthma in the absence of FcγRIIB or FcγRI/FcγRIII signaling. We found that suppression of Th2 cell activity, allergic inflammation, and allergen-specific IgE responses is independent of FcγRIIB and FcγRI/FcγRIII signaling. Moreover, we show that the IT-induced allergen-specific systemic IgG or IgA responses and B cell function are dispensable for suppression of the late-phase allergic response by IT treatment. Finally, we found that the secretory mucosal IgA response also is not required for suppression of the Th2-driven allergic inflammation by IT. These data are in contrast to the suppression of the immediate phase of the allergic response, which is critically dependent on the induced allergen-specific serum IgG response. Hence, IT-induced suppression of the immediate and late phases of the allergic response is governed by divergent and independent mechanisms. Our data show that the IT-induced suppression of the Th2 cell-dependent late-phase allergic response is independent of the allergen-specific IgG and IgA responses that are associated with IT treatment.

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Predictive value of venom‐specific IgE, IgG and IgG subclass antibodies in patients on immunotherapy with honey bee venom

Cited by 151 publications

References 21 publications

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

IL-10 and Regulatory T Cells Cooperate in Allergen-Specific Immunotherapy To Ameliorate Allergic Asthma

The IgE-facilitated allergen binding (FAB) assay: Validation of a novel flow-cytometric based method for the detection of inhibitory antibody responses

Suppression of Th2-Driven Airway Inflammation by Allergen Immunotherapy Is Independent of B Cell and Ig Responses in Mice

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