Publications by authors named "Louisa K Wilcock"

4 Publications

  • Page 1 of 1

Grass pollen immunotherapy induces an allergen-specific IgA2 antibody response associated with mucosal TGF-beta expression.

J Immunol 2007 Apr;178(7):4658-66

Upper Respiratory Medicine, Section of Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College, Dovehouse Street, London, U.K.

Allergen immunotherapy (IT) has long-term efficacy in IgE-mediated allergic rhinitis and asthma. IT has been shown to modify lymphocyte responses to allergen, inducing IL-10 production and IgG Abs. In contrast, a putative role for IgA and local TGF-beta-producing cells remains to be determined. In 44 patients with seasonal rhinitis/asthma, serum IgA1, IgA2, and polymeric (J chain-containing) Abs to the major allergen Phl p 5 were determined by ELISA before and after a 2-year double-blind trial of grass pollen (Phleum pratense) injection IT. Nasal TGF-beta expression was assessed by in situ hybridization. Sera from five IT patients were fractionated for functional analysis of the effects of IgA and IgG Abs on IL-10 production by blood monocytes and allergen-IgE binding to B cells. Serum Phl p 5-specific IgA2 Abs increased after a 2-year treatment (approximately 8-fold increase, p = 0.002) in contrast to IgA1. Increases in polymeric Abs to Phl p 5 (approximately 2-fold increase, p = 0.02) and in nasal TGF-beta mRNA (p = 0.05) were also observed, and TGF-beta mRNA correlated with serum Phl p 5 IgA2 (r = 0.61, p = 0.009). Post-IT IgA fractions triggered IL-10 secretion by monocytes while not inhibiting allergen-IgE binding to B cells as observed with IgG fractions. This study shows for the first time that the IgA response to IT is selective for IgA2, correlates with increased local TGF-beta expression, and induces monocyte IL-10 expression, suggesting that IgA Abs could thereby contribute to the tolerance developed in IT-treated allergic patients.
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http://dx.doi.org/10.4049/jimmunol.178.7.4658DOI Listing
April 2007

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

J Immunol Methods 2006 Dec 5;317(1-2):71-9. Epub 2006 Oct 5.

Upper Respiratory Medicine, Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, Dovehouse Street, London, SW3 6LY, UK.

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. The 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 the 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 a specific method suitable as a tool for monitoring inhibitory antibody function from patients receiving allergen immunotherapy.
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http://dx.doi.org/10.1016/j.jim.2006.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934503PMC
December 2006

IgE-facilitated antigen presentation: role in allergy and the influence of allergen immunotherapy.

Immunol Allergy Clin North Am 2006 May;26(2):333-47, viii-ix

Upper Respiratory Medicine, Imperial College, National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK.

IgE-facilitated allergen presentation (FAP) is an important pathogenic mechanism in allergic disease and represents a potential therapeutic target. Allergen immunotherapy is a highly effective therapy, particularly in patients with seasonal pollinosis who fail to respond to usual pharmacotherapy. Allergen immunotherapy induces "blocking" IgG antibodies that are detectable in serum and have been shown to inhibit IgE-FAP in vitro. This review summarizes the main components involved in IgE-FAP and the potential value of a validated functional assay of serum inhibitory antibodies for IgE-FAP for monitoring the clinical response to immunotherapy.
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http://dx.doi.org/10.1016/j.iac.2006.02.004DOI Listing
May 2006

Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity.

J Immunol 2004 Mar;172(5):3252-9

Upper Respiratory Medicine, Imperial College London, National Heart and Lung Institute, London, United Kingdom.

T regulatory cells and IL-10 have been implicated in the mechanism of immunotherapy in patients with systemic anaphylaxis following bee stings. We studied the role of IL-10 in the induction of clinical, cellular, and humoral tolerance during immunotherapy for local mucosal allergy in subjects with seasonal pollinosis. Local and systemic IL-10 responses and serum Ab concentrations were measured before/after a double-blind trial of grass pollen (Phleum pratense, Phl P) immunotherapy. We observed local increases in IL-10 mRNA-positive cells in the nasal mucosa after 2 years of immunotherapy, but only during the pollen season. IL-10 protein-positive cells were also increased and correlated with IL-10 mRNA(+) cells. These changes were not observed in placebo-treated subjects or in healthy controls. Fifteen and 35% of IL-10 mRNA signals were colocalized to CD3(+) T cells and CD68(+) macrophages, respectively, whereas only 1-2% of total CD3(+) cells and 4% of macrophages expressed IL-10. Following immunotherapy, peripheral T cells cultured in the presence of grass pollen extract also produced IL-10. Immunotherapy resulted in blunting of seasonal increases in serum allergen Phl p 5-specific IgE, 60- to 80-fold increases in Phl p 5-specific IgG, and 100-fold increases in Phl p 5-specific IgG4. Post-immunotherapy serum exhibited inhibitory activity, which coeluted with IgG4, and blocked IgE-facilitated binding of allergen-IgE complexes to B cells. Both the increases in IgG and the IgG "blocking" activity correlated with the patients' overall assessment of improvement. Thus, grass pollen immunotherapy may induce allergen-specific, IL-10-dependent "protective" IgG4 responses.
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http://dx.doi.org/10.4049/jimmunol.172.5.3252DOI Listing
March 2004
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