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

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Presentation on theme: "Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy  Ravi S. Swamy, MD, Neha Reshamwala,"— Presentation transcript:

1 Epigenetic modifications and improved regulatory T-cell function in subjects undergoing dual sublingual immunotherapy  Ravi S. Swamy, MD, Neha Reshamwala, MD, Tessa Hunter, BSc, Soujanya Vissamsetti, MD, Carah B. Santos, MD, Fuad M. Baroody, MD, Peter H. Hwang, MD, Elisabeth G. Hoyte, NP, Marco A. Garcia, BSc, Kari C. Nadeau, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 130, Issue 1, Pages e7 (July 2012) DOI: /j.jaci Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 Clinical efficacy of dual SLIT. A and B, Rhinoconjunctivitis symptom scores (RCS; Fig 1, A) and medication use scores (MS; Fig 1, B). C, Responses to skin prick test challenges. D, NDCs to TG at 18 months. The orange circle denotes tolerant subjects. ∗∗P < .01 and ∗∗∗P < Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 Change from baseline in mean antibody levels for TG-specific humoral responses. Phl p 5–specific IgE (A) and IgG4 (B) responses from serum collected at baseline and at various time points from dual SLIT–treated subjects (squares, n = 20) or placebo-treated subjects (circles, n = 10) is shown. ∗P < .05. GPS, Grass allergy season; mgA, milligrams of antigen-specific antibody. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Decreased basophil activation from subjects receiving dual immunotherapy. Expression of CD203c levels on basophils stimulated with TG, DM, and oak from subjects before therapy (Pre) and after (Post) 24 months of dual SLIT (A-C) or placebo (D-F) is shown ∗∗∗P < NS, Not significant: P = .08; MFI, mean fluorescence intensity. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Memory Treg cells from dual SLIT–treated subjects suppress allergen-specific T-cell responses. Treg cell–suppressive activity of total mixed Treg cells from dual SLIT–treated subjects (A), memory Treg cells from dual SLIT–treated subjects (B), total mixed Treg cells from placebo-treated subjects (C), or total Teff cell proliferation (D) before (pre) and after (post) treatment is shown. ∗P < .05. NS, Not significant. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Epigenetic regulation of Foxp3 in Treg cells from subjects treated with dual SLIT. A, CpG methylation of purified memory or naive Treg cells from subjects before (Pre) and 12 months after (Post) therapy. B, Analysis of Foxp3 transcript from memory Treg cells. Foxp3 transcription levels are shown as relative fold increase over expression of the housekeeping gene β-glucuronidase. ∗P < .05. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

7 Fig 6 Increased memory Treg cells in tolerized subjects. Longitudinal analysis of memory CD4+CD25highCD127loCD45RO+CD62L−Foxp3+ Treg cells from tolerant (circles, n = 7) and desensitized (squares, n = 9) subjects after dual SLIT is shown. ∗P < .05. mo, Months after baseline. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

8 Fig 7 Expression profiles of Treg cell markers in tolerant subjects. A and B, Expression of Treg cell markers on memory or naive Treg cells purified from dual SLIT–treated subjects (Fig 7, A) or placebo-treated subjects (Fig 7, B) before (pre) and 12 months after (post) treatment. ∗P < .05 for PD-1, IL-10, and Foxp3. C, Baseline expression levels from memory Treg cells from subjects who became tolerized (n = 7) or desensitized (n = 9). Gzm B, Granzyme B; MFI, mean fluorescence intensity. Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

9 Fig E1 Flow diagram of study design.
Journal of Allergy and Clinical Immunology  , e7DOI: ( /j.jaci ) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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