Presentation is loading. Please wait.

Presentation is loading. Please wait.

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

Published byAda Karlsen Modified over 6 years ago

Similar presentations

Presentation on theme: "Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies  Louisa K. James, PhD, Mohamed H. Shamji,"— Presentation transcript:

1 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 e5 (February 2011) DOI: /j.jaci Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 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  , e5DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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

Similar presentations

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

Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy  Erik Wambre, PhD, Jonathan.
Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy  Ravi S. Swamy, MD, Neha Reshamwala,

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,

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.

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 

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,

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

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,

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.

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,

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,

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.

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.

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.

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,

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,

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.

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.

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 

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.

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

Similar presentations

Ads by Google