Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies Louisa K. James, PhD, Mohamed H. Shamji,

Slides:

Advertisements

Similar presentations

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy Erik Wambre, PhD, Jonathan.

Advertisements

Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy Ravi S. Swamy, MD, Neha Reshamwala,

Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms Anna Slovick, MRCS, Abdel Douiri, PhD,

Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses Giuseppina Rotiroti, MD, Mohamed Shamji, PhD, Stephen.

Comparison of the immunogenicity of BM32, a recombinant hypoallergenic B cell epitope–based grass pollen allergy vaccine with allergen extract–based vaccines

Birch pollen–related food allergy: Clinical aspects and the role of allergen-specific IgE and IgG4 antibodies Marija Geroldinger-Simic, MD, Thomas Zelniker,

Kuan-Wei Chen, PhD, Katharina Blatt, MSc, Wayne R

A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy Satya D. Narisety,

SQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial Stephen.

High-titer IgE antibody specific for pollen allergens in northern California is associated with both wheezing and total serum IgE Elizabeth A. Erwin,

Lolium perenne peptides for treatment of grass pollen allergy: A randomized, double- blind, placebo-controlled clinical trial Mohamed H. Shamji, PhD,

Correlation of allergen-specific T follicular helper cell counts with specific IgE levels and efficacy of allergen immunotherapy Yin Yao, MD, Cai-Ling.

Tolerant beekeepers display venom-specific functional IgG4 antibodies in the absence of specific IgE Eva-Maria Varga, MD, Fahima Kausar, MSc, Werner.

Giant ragweed specific immunotherapy is not effective in a proportion of patients sensitized to short ragweed: Analysis of the allergenic differences.

Randomized controlled trial of a ragweed allergy immunotherapy tablet in North American and European adults Peter S. Creticos, MD, Jennifer Maloney,

Anaphylaxis to wheat isolates: Immunochemical study of a case proved by means of double-blind, placebo-controlled food challenge Virginie Leduc, PhD,

Epicutaneous allergen-specific immunotherapy ameliorates grass pollen–induced rhinoconjunctivitis: A double-blind, placebo-controlled dose escalation.

Blocking antibodies induced by immunization with a hypoallergenic parvalbumin mutant reduce allergic symptoms in a mouse model of fish allergy Raphaela.

Birch pollen immunotherapy results in long-term loss of Bet v 1–specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies

A randomized, double-blind, placebo-controlled study of omalizumab combined with oral immunotherapy for the treatment of cow's milk allergy Robert A.

SQ-standardized sublingual grass immunotherapy: Confirmation of disease modification 2 years after 3 years of treatment in a randomized trial Stephen.

Grass pollen immunotherapy inhibits allergen-induced infiltration of CD4+ T lymphocytes and eosinophils in the nasal mucosa and increases the number of.

Suzana Radulovic, MD, Mikila R. Jacobson, PhD, Stephen R

Activated glycoprotein A repetitions predominant (GARP)–expressing regulatory T cells inhibit allergen-induced intestinal inflammation in humanized mice

Antibody conjugates bispecific for intercellular adhesion molecule 1 and allergen prevent migration of allergens through respiratory epithelial cell layers

Comparison of the immunogenicity of BM32, a recombinant hypoallergenic B cell epitope–based grass pollen allergy vaccine with allergen extract–based vaccines

Safety and efficacy in children of an SQ-standardized grass allergen tablet for sublingual immunotherapy Albrecht Bufe, PhD, MD, Peter Eberle, MD, Eivy.

Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation

In vivo allergenic activity of a hypoallergenic mutant of the major fish allergen Cyp c 1 evaluated by means of skin testing Nikolaos Douladiris, MD,

Response to sublingual immunotherapy with grass pollen extract: Monotherapy versus combination in a multiallergen extract Sheila M. Amar, MD, Ronald.

Oliver T. Burton, PhD, Jaciel M. Tamayo, PhD, Amanda J

Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms Anna Slovick, MRCS, Abdel Douiri, PhD,

Mohamed H. Shamji, PhD, Janice A. Layhadi, MSc, Guy W

Human mast cells drive memory CD4+ T cells toward an inflammatory IL-22+ phenotype Nicolas Gaudenzio, PhD, Camille Laurent, MD, Salvatore Valitutti,

IgG4 inhibits peanut-induced basophil and mast cell activation in peanut-tolerant children sensitized to peanut major allergens Alexandra F. Santos,

“Auto-anti-IgE”: Naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation Yih-Chih Chan, PhD, Faruk Ramadani, PhD,

A randomized, double-blind, placebo-controlled pilot study of sublingual versus oral immunotherapy for the treatment of peanut allergy Satya D. Narisety,

Short-term subcutaneous grass pollen immunotherapy under the umbrella of anti–IL-4: A randomized controlled trial Adam M. Chaker, MD, Mohamed H. Shamji,

Thymic stromal lymphopoietin–activated invariant natural killer T cells trigger an innate allergic immune response in atopic dermatitis Wen Hao Wu, PhD,

Role of IL-35 in sublingual allergen immunotherapy

Genetically engineered hybrid proteins from Parietaria judaica pollen for allergen- specific immunotherapy Roberto González-Rioja, PhD, Ignacio Ibarrola,

Allergen-specific immunotherapy with recombinant grass pollen allergens Marek Jutel, MD, Lothar Jaeger, MD, Roland Suck, PhD, Hanns Meyer, Dipl Math,

Grass tablet sublingual immunotherapy downregulates the TH2 cytokine response followed by regulatory T-cell generation Abel Suárez-Fueyo, PhD, Tania.

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy Erik Wambre, PhD, Jonathan.

Kuan-Wei Chen, PhD, Katharina Blatt, MSc, Wayne R

Sublingual immunotherapy with once-daily grass allergen tablets: A randomized controlled trial in seasonal allergic rhinoconjunctivitis Stephen R. Durham,

Allergen specificity of IgG4-expressing B cells in patients with grass pollen allergy undergoing immunotherapy Louisa K. James, PhD, Holly Bowen, PhD,

Direct ex vivo analysis of allergen-specific CD4+ T cells

Mohamed H. Shamji, PhD, FAAAI, Stephen R. Durham, MD, FRCP

Association between specific timothy grass antigens and changes in TH1- and TH2-cell responses following specific immunotherapy Véronique Schulten, PhD,

Is intralymphatic immunotherapy ready for clinical use in patients with grass pollen allergy? Marianne Witten, MD, PhD, Hans-Jørgen Malling, MD, Lars.

Luisa Lunardon, MD, Aimee S. Payne, MD, PhD

CD23 surface density on B cells is associated with IgE levels and determines IgE- facilitated allergen uptake, as well as activation of allergen-specific.

Sara Paveglio, PhD, MS, Erin Bennett, MS, Kelly L. Hawley, PhD, Adam P

Sublingual grass allergen tablet immunotherapy provides sustained clinical benefit with progressive immunologic changes over 2 years Ronald Dahl, MD,

Birch pollen–related food allergy: Clinical aspects and the role of allergen-specific IgE and IgG4 antibodies Marija Geroldinger-Simic, MD, Thomas Zelniker,

Long-term clinical efficacy in grass pollen–induced rhinoconjunctivitis after treatment with SQ-standardized grass allergy immunotherapy tablet Stephen.

Mechanism of TH2/TH17-predominant and neutrophilic TH2/TH17-low subtypes of asthma Weimin Liu, PhD, Sucai Liu, PhD, Mukesh Verma, PhD, Iram Zafar, MS,

In vivo effects of glucocorticoids on IgE production

Pedro Gamboa, MD, PhD, Rosa Sanchez-Monge, PhD, M

Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity James N. Francis, PhD, Louisa.

IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen exposure: Effect of immunotherapy Kayhan T. Nouri-Aria, PhD, FRCPath, Charles.

Julie Negri, BA, S. Brandon Early, BA, John W

Repeated low-dose intradermal allergen injection suppresses allergen-induced cutaneous late responses Giuseppina Rotiroti, MD, Mohamed Shamji, PhD, Stephen.

Placental transfer of allergen-specific IgG but not IgE from a specific immunotherapy– treated mother Sabine Flicker, PhD, Katharina Marth, MD, Heinz.

Lolium perenne peptides for treatment of grass pollen allergy: A randomized, double- blind, placebo-controlled clinical trial Mohamed H. Shamji, PhD,

Combination treatment with omalizumab and rush immunotherapy for ragweed-induced allergic rhinitis: Inhibition of IgE-facilitated allergen binding Sven.

Allergen specificity of IgG4-expressing B cells in patients with grass pollen allergy undergoing immunotherapy Louisa K. James, PhD, Holly Bowen, PhD,

Double-blind, placebo-controlled study with a modified therapeutic vaccine of Salsola kali (Russian thistle) administered through use of a cluster schedule

In vitro assays for the diagnosis of IgE-mediated disorders

Presentation transcript:

Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies Louisa K. James, PhD, Mohamed H. Shamji, PhD, Samantha M. Walker, PhD, RGN, Duncan R. Wilson, MD, FRCP, Petra A. Wachholz, PhD, James N. Francis, PhD, Mikila R. Jacobson, PhD, Ian Kimber, PhD, Stephen J. Till, PhD, MRCP, Stephen R. Durham, MD, FRCP Journal of Allergy and Clinical Immunology Volume 127, Issue 2, Pages 509-516.e5 (February 2011) DOI: 10.1016/j.jaci.2010.12.1080 Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Study design and pollen counts. A, Weekly average grass pollen counts. B, Forty-four patients with hay fever were monitored for 1 pollen season and then randomized to receive subcutaneous allergen-specific immunotherapy or placebo injections for 2 years. Thirteen patients who received active treatment consented to a further 2-year, randomized, double-blind discontinuation of immunotherapy. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 CD23-mediated IgE-FAB. A and B, Allergen-IgE complexes bound to EBV-transformed B cells were detected by means of flow cytometry (Fig 2, A) and laser scanning microscopy (Fig 2, B). C, CD23 receptor coaggregation was visualized in the presence or absence of grass pollen allergen. Data shown are representative results from 3 independent experiments. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Long-term clinical improvement after discontinuation of immunotherapy is associated with persistent IgG-associated blocking activity but not total allergen-specific IgG4 antibodies. A, Symptom and medication scores. B, Serum inhibitory activity for allergen-IgE binding to B cells. C and D, P pratense–specific IgG1 (Fig 3, C) and IgG4 (Fig 3, D) antibodies measured by means of ELISA. E, Representative example of IgE-FAB in the presence of preimmunotherapy and postimmunotherapy serum. CSMS, Combined Symptoms and Rescue Medication Scores; FITC, fluorescein isothiocyanate; IT, immunotherapy. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Inhibitory P pratense–specific antibodies disrupt IgE binding and CD23 distribution on B cells. A, IgE immunostaining. B, Quantification of beading pattern (IgE+ B cells). C, CD23 receptor immunostaining. D, Quantification of beading pattern (CD23+ B cells). Controls (without P pretense) are represented by open circles. Allergen alone had no effect on B cells (data not shown). FITC, Fluorescein isothiocyanate; IT, immunotherapy. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 Inhibition of allergen-IgE complex binding is IgG4 dependent. A, IgG4-containing sera versus IgG4-depleted sera. B and C, Representative examples of allergen-IgE complex binding in the presence of preimmunotherapy and postimmunotherapy serum compared with postimmunotherapy serum depleted of IgG4 antibodies (D). FITC, Fluorescein isothiocyanate. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Visualization of CD23 receptor coaggregation and allergen-IgE complexes binding to B cells. Serum from a subject with grass allergy (P pratense–specific IgE >100 IU/L) was incubated with 1 μg/mL P pratense extract in the presence of preimmunotherapy serum. CD23-enriched EBV-transformed B cells were incubated with the complexes. Cells were immunostained with fluorescein isothiocyanate–labeled rabbit polyclonal anti-human IgE antibody and phycoerythrin-labeled antihuman CD23 antibody. A, A bright field image of the cells is shown. B, Allergen-IgE complexes were visualized as IgE+ staining. C, Clustering of CD23 receptors were visualized as a beading pattern. D, Colocalization of CD23-IgE-allergen complexes with dual staining of CD23 receptor and allergen-IgE complexes. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

CD23-dependent allergen binding with freshly purified B cells CD23-dependent allergen binding with freshly purified B cells. IgE-FAB to B cells isolated from PBMCs was measured by using sera from preimmunotherapy (n = 5) and postimmunotherapy (n = 5) subjects. Addition of postimmunotherapy serum resulted in a significant decrease of allergen-IgE complexes binding to B cells isolated from PBMCs. P values represent statistical differences within groups, as determined by using the Wilcoxon matched-pairs test. IT, Immunotherapy. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Persistence of functional P pratense–specific IgG-dependent inhibitory antibody activity after discontinuation of grass pollen immunotherapy. A, Serum-inhibitory activity for allergen-IgE binding to B cells. B, P pratense–specific IgG antibodies measured by using ELISA. These data were obtained from a second cohort of patients who underwent discontinuation of grass pollen immunotherapy. Originally described in Durham et al.8 IT, Immunotherapy. Journal of Allergy and Clinical Immunology 2011 127, 509-516.e5DOI: (10.1016/j.jaci.2010.12.1080) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions