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

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Presentation transcript:

Birch pollen immunotherapy results in long-term loss of Bet v 1–specific TH2 responses, transient TR1 activation, and synthesis of IgE-blocking antibodies Christian Möbs, PhD, Henrik Ipsen, MSc, Lea Mayer, DDS, Caroline Slotosch, MD, Arnd Petersen, PhD, Peter A. Würtzen, PhD, Michael Hertl, MD, Wolfgang Pfützner, MD Journal of Allergy and Clinical Immunology Volume 130, Issue 5, Pages 1108-1116.e6 (November 2012) DOI: 10.1016/j.jaci.2012.07.056 Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 ELISpot analysis of Bet v 1–specific IL-5–, IFN-γ–, and IL-10–producing T cells during a 54-month (m0-m54) observation period including SIT with birch pollen extract and a follow-up phase after cessation of treatment (post-SIT). Median values are indicated by black lines. Birch pollen seasons are highlighted in gray. Discontinuities by dashed lines mark nonexistent data. Differences between initiation of SIT and during/after SIT were analyzed by using the nonparametric Wilcoxon signed-rank test. *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 A-C, Birch pollen–specific IgE (Fig 2, A), total IgG (Fig 2, B), and IgG4 (Fig 2, C) concentrations determined out of and during the birch pollen season (highlighted in gray) in patients with birch pollen allergy treated with SIT and after SIT (post-SIT). D, IgE/IgG ratio over the entire 54-month observation period. Median values are indicated by black lines. Discontinuities by dashed lines mark nonexistent data. Differences in pretreatment values compared with subsequent time points were analyzed by using the nonparametric Wilcoxon signed-rank test. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Bet v 1–specific IgG1 and IgG4 antibody levels (17 kDa) monitored in SIT-treated patients' sera by means of Western blotting at initiation of (I), end of (E), and after (P) SIT (m42 or m54 as indicated). M, Marker; Neg-C, serum of a healthy subject; Pos-C, serum of a patient with birch pollen allergy; Tris-C, buffer control. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 A, Analysis of allergen-IgE complex formation in SIT-treated patients with birch pollen allergy by using the FAP assay. The data from all patients is expressed as a percentage of the pretreatment value. B, Inhibitory capacity of treatment-induced non-IgE antibodies evaluated by using the IgE-blocking factor assay. Data are shown as a ratio of IgE binding to allergen in the presence of allergen-specific non-IgE antibodies divided by IgE binding alone. Median values are indicated by black lines. Birch pollen seasons are highlighted in gray. Discontinuities by dashed lines mark nonexistent data. Differences in pretreatment values compared with subsequent time points were analyzed by using the nonparametric Wilcoxon signed-rank test. *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 5 A, Inverse relationship between allergen-specific IgG antibody concentrations and IgE-blocking factor in individual SIT-treated patients for up to 54 months. B, Comparison of mock-treated (IgG+) and IgG-depleted (IgG−) plasma samples from 5 patients with birch pollen allergy before initiation of SIT (pre-SIT) and at different time points (months 6, 18, 24, 30, and 36) during SIT, as evaluated by using ImmunoCAP analysis. C, IgE-blocking factor analysis of mock-treated (IgG+) and IgG-depleted (IgG−) plasma samples of 5 SIT-treated patients before initiation of treatment (pre-SIT) and during SIT. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E1 Specific IL-5 (A), IFN-γ (B), and IL-10 (C) production by PBMCs stimulated with rBet v 1. Cytokine levels were measured during 30 months (circles; m0-m30) of specific SIT and a post-SIT phase showing individual results at the last visit after termination of treatment (squares, month 42; triangles, month 54). Median values are indicated by black lines. Birch pollen seasons are highlighted in gray. Differences between initiation of SIT and during/after SIT were analyzed by using the nonparametric Wilcoxon signed-rank test. *P < .05 and **P < .01. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E2 Bet v 1–specific IgE antibody concentrations determined out of and during the birch pollen season (highlighted in gray) in patients with birch pollen allergy treated with SIT and after cessation of treatment (post-SIT). Median values are indicated by black lines. Discontinuities by dashed lines mark nonexistent data. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E3 Birch pollen–specific IgE/IgG4 ratios determined out of and during the birch pollen season (highlighted in gray) in patients with birch pollen allergy treated with SIT and after cessation of treatment (post-SIT). Median values are indicated by black lines. Discontinuities by dashed lines mark nonexistent data. Differences in pretreatment values compared with subsequent time points were analyzed by using the nonparametric Wilcoxon signed-rank test. *P < .05, **P < .01, and ***P < .001. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig E4 nBet v 1–specific (A) and birch pollen extract–specific IgG1 and IgG4 antibody levels (B) monitored in SIT-treated patients' sera by means of Western blotting. Concomitant alterations in IgG1 and IgG4 levels were detectable comparing initiation of (I), end of (E), and time points after (P) SIT (month 42 or 54, as indicated). M, Marker; Neg-C, serum of a healthy subject; Pos-C, serum of a patient with birch pollen allergy; Tris-C, buffer control. Journal of Allergy and Clinical Immunology 2012 130, 1108-1116.e6DOI: (10.1016/j.jaci.2012.07.056) Copyright © 2012 American Academy of Allergy, Asthma & Immunology Terms and Conditions