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

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Presentation on theme: "Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms  Anna Slovick, MRCS, Abdel Douiri, PhD,"— Presentation transcript:

1 Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms  Anna Slovick, MRCS, Abdel Douiri, PhD, Rachel Muir, RN, PhD, Andrea Guerra, MD, Konstantinos Tsioulos, MRCS, Evie Hay, BSc, Emily P.S. Lam, PhD, Joanna Kelly, MSc, Janet L. Peacock, PhD, Sun Ying, MD, PhD, Mohamed H. Shamji, PhD, David J. Cousins, PhD, Stephen R. Durham, MD, FRCP, Stephen J. Till, PhD, FRCP  Journal of Allergy and Clinical Immunology  Volume 139, Issue 6, Pages e13 (June 2017) DOI: /j.jaci Copyright © 2016 The Authors Terms and Conditions

2 Fig 1 Study design. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

3 Fig 2 CONSORT diagram. All randomized participants were included in the intention-to-treat (ITT) analysis. Only participants who adequately adhered to treatment and rescue medications were included in the per-protocol analysis. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

4 Fig 3 Primary outcome and nasal symptoms. A, Mean daily combined symptom and medication scores in the primary intention-to-treat analysis. Broken vertical lines indicate the beginning and end of the peak pollen season (June 12 to July 26, 2013). B, Daily grass pollen counts in central London during the 2013 grass pollen season. C, Mean daily nasal symptom scores (sum of scores for sneezing, blockage, and running). D, Mean nasal symptoms measured by using a VAS (total of blockage, running, itching, and sneezing). AUC values for each participant were compared according to treatment arm. P values are based on the Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

5 Fig 4 Immunologic outcomes. A, Levels of P pratense–specific IgE and IgG before and after completion of 7 intradermal allergen or histamine control injections. B, Expression of CRTH2 (TH2 marker) and CXCR3 (TH1 marker) on CD4+ cells expanded from skin biopsy specimens (24 hours after skin challenge). C, Areas of cutaneous late-phase responses (24 hours after intradermal skin challenge) 4 months and either 7, 10, or 13 months after treatment (September 2013). Late-phase response suppression was shown in our previous study (Rotiroti et al5) immediately after 6 biweekly intradermal injections. Solid bars represent median values. P values for pretreatment and posttreatment serology comparisons are based on the Wilcoxon signed-rank test, and those for between-group IgE and IgG levels are based on analysis of covariance. P values in Fig 4, B and C, are based on the Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

6 Fig E1 Effects of intradermal immunotherapy on Phl p 5– (A) and Phl p 1– (B) specific IgE. Levels of IgE specific for the major allergens Phl p 5 and Phl p 1 before and after completion of 7 intradermal allergen or histamine control injections are shown. P values for pretreatment and posttreatment comparisons were based on the Wilcoxon signed-rank test. P values for between-group comparisons were based on analysis of covariance. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

7 Fig E2 Flow cytometric analysis of CD4+ T cells from skin biopsy explants. Representative flow cytometric plots illustrating surface staining for CCR6, CXCR3, and CRTH2 gated on skin biopsy-derived CD4+ T cells in a participant who received histamine control (left) and a participant who received grass pollen intradermal injections (right) are shown. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

8 Fig E3 Heat map showing expression of selected genes associated with TH1/TH2 phenotypes and allergic inflammatory responses. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

9 Fig E4 Basophil activation tests. Percentages of basophils staining positive for the activation markers CD63 (A), CD107a (B), and CD203c (C) are shown. Whole blood was stimulated under the conditions shown. P values are based on the Mann-Whitney U test. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

10 Fig E5 Immunohistochemistry analysis of skin biopsy specimens. Comparison of allergen-induced inflammatory cell numbers in skin biopsy specimens from intradermal immunotherapy and control arm participants. Data shown indicate numbers of neutrophils (A), eosinophils (B), CD3+ cells (C), and CD4+ cells (D) in skin biopsy specimens taken after diluent and P Pratense intradermal skin challenges in September Cells were stained by using the APAAP method. Solid bars represent median values. P values comparing diluent- and allergen-challenged biopsy specimens are based on the Wilcoxon signed-rank test. P values for between-group comparisons are based on analysis of covariance. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

11 Fig E6 Lymphangitis in a participant who received active intradermal immunotherapy. The photograph was taken 40 minutes after intradermal injection. Journal of Allergy and Clinical Immunology  , e13DOI: ( /j.jaci ) Copyright © 2016 The Authors Terms and Conditions

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