A double‐blind, placebo‐controlled birch allergy vaccination study: inhibition of CD23‐mediated serum‐immunoglobulin E‐facilitated allergen presentation

Neerven, R. J. Joost van; Arvidsson, Monica; Ipsen, Henrik; Sparholt, S.H.; Rak, S.; Würtzen, Peter Adler

doi:10.1111/j.1365-2222.2004.01899.x

Cited by 76 publications

(68 citation statements)

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“…Interference with these IgE-dependent mechanisms by 'blocking' IgG antibodies may down regulate T cell responses and manifest as a reduction in allergic responses in vivo. Previous studies have shown that serum obtained from subjects following birch immunotherapy was able to inhibit IgE-facilitated presentation of allergen by B cells to an allergen-specific T cell clone (van Neerven et al, 1999,van Neerven et al, 2004. We have previously demonstrated that serum obtained from patients receiving grass pollen immunotherapy can inhibit IgE-facilitated allergen presentation to a grass-specific T lymphocyte clone (Wachholz et al, 2003).…”

Section: Introductionmentioning

confidence: 82%

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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Section: Introductionmentioning

confidence: 82%

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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“…In an autologous in vitro system, in which B and T cells were derived from a patient with atopic dermatitis, patient serum containing IgE anti-Der p II (major house dust mite) facilitated Ag presentation by EBV-immortalized B cells to Th cells (36). Allergen-specific IgG, induced by specific immunotherapy, was shown to compete with allergen-specific IgE from patients undergoing treatment, and lead to reduced IgE/CD23-facilitated allergen presentation (54,67,68). This indicates that IgEmediated allergen presentation may be of clinical relevance.…”

Section: Discussionmentioning

confidence: 99%

IgE Enhances Antibody and T Cell Responses In Vivo via CD23+ B Cells

Getahun

Hjelm

Heyman

2005

The Journal of Immunology

101

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IgE Abs, passively administered together with their specific Ag, can enhance the production of Abs recognizing this Ag by >100-fold. IgE-mediated feedback enhancement requires the low affinity receptor for IgE, CD23. One possible mechanism is that B cells take up IgE-Ag via CD23 and efficiently present Ag to Th cells, resulting in better Ab responses. To test whether IgE Abs have an effect on Th cells in vivo, mice were adoptively transferred with CD4+ T cells expressing a transgenic OVA-specific TCR, before immunization with IgE anti-TNP (2,4,6-trinitrophenyl) plus OVA-TNP or with OVA-TNP alone. IgE induced a 6- to 21-fold increase in the number of OVA-specific T cells. These cells acquired an activated phenotype and were visible in splenic T cell zones. The T cell response peaked 3 days after immunization and preceded the OVA-specific Ab response by a few days. Transfer of CD23+ B cells to CD23-deficient mice rescued their ability to respond to IgE-Ag. Interestingly, in this situation also CD23-negative B cells produce enhanced levels of OVA-specific Abs. The data are compatible with the Ag presentation model and suggest that B cells can take up Ag via “unspecific” receptors and activate naive T cells in vivo.

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“…Evidence for the induction of allergen-specific Tregs during SLIT is limited [14], but convincing increases in allergen-specific IgG 4 have been observed [15][16][17]. Post-immunotherapy sera from SCITtreated patients have been shown to inhibit IgE-facilitated allergen binding to B cells and subsequent presentation to allergen-specific T cell clones [18][19][20]. The proliferative response of these T cell clones corresponds to the level of allergen-IgE binding to B cells, which can be determined by flow cytometry in a validated technique termed the IgE-facilitated allergen binding (IgE-FAB) assay [21].…”

Section: Clinical Mechanisms In Allergic Diseasementioning

confidence: 99%

Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3‐expressing cells and elevated allergen‐specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E‐facilitated allergen binding to B cells

Scadding

Shamji

Jacobson

et al. 2010

Clin Experimental Allergy

230

177

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SummaryBackground The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). Objectives To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB). Methods Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebotreated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-b mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT. Results Foxp31 cells were increased in the oral epithelium of SLIT-vs. placebo-treated atopics (P = 0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P = 0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT-compared with placebo-treated atopics (P = 0.1 for both). IgG 1 and IgG 4 were increased following SLIT (Po0.001). Peak seasonal IgA 1 and IgA 2 were increased during SLIT (Po0.05). There was a time-dependent increase in serum inhibitory activity for IgE-FAB in SLIT-treated atopics.Conclusions SLIT with grass pollen extract is associated with increased Foxp3 1 cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.

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A double‐blind, placebo‐controlled birch allergy vaccination study: inhibition of CD23‐mediated serum‐immunoglobulin E‐facilitated allergen presentation

Cited by 76 publications

References 50 publications

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

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

IgE Enhances Antibody and T Cell Responses In Vivo via CD23+ B Cells

Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3‐expressing cells and elevated allergen‐specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E‐facilitated allergen binding to B cells

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