Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms

Anna Slovick; Abdel Douiri; Rachel Muir; Andrea Guerra; Konstantinos Tsioulos; Evie Hay; Emily P.S. Lam; Joanna Kelly; Janet L. Peacock; Ying Sun; Mohamed H. Shamji; David J. Cousins; Stephen R. Durham; Stephen J. Till

doi:10.1016/j.jaci.2016.09.024

Intradermal grass pollen immunotherapy increases T_H2 and IgE responses and worsens respiratory allergic symptoms

Anna Slovick, Abdel Douiri, Rachel Muir, Andrea Guerra, Konstantinos Tsioulos, Evie Hay, Emily P.S. Lam, Joanna Kelly, Janet L. Peacock, Ying Sun, Mohamed H. Shamji, David J. Cousins, Stephen R. Durham, Stephen J. Till^*

^*Corresponding author for this work

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Abstract

Background: Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy. Objective: We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis.

Methods: We randomly assigned 93 adults with grass pollen-induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment.

Results: There was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, -172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, -11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense-specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the T_H2 surface marker CRTH2 (P = .04) and lower expression of the T_H1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03).

Conclusion: Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.

Original language	English
Pages (from-to)	1830-1839
Number of pages	10
Journal	Journal of Allergy and Clinical Immunology
Volume	139
Issue number	6
Early online date	20 Oct 2016
DOIs	https://doi.org/10.1016/j.jaci.2016.09.024
Publication status	Published - Jun 2017

Keywords

Allergy immunotherapy
allergic rhinitis
grass pollen
Phleum Pratense
immunotherapy
intradermal
low-dose

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Intradermal grass pollen immunotherapy_SLOVICK_Accepted 19Sep2016 GOLD CorrectedProofAccepted author manuscript, 3.34 MBLicence: CC BY

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Slovick, A., Douiri, A., Muir, R., Guerra, A., Tsioulos, K., Hay, E., Lam, E. P. S., Kelly, J., Peacock, J. L., Sun, Y., Shamji, M. H., Cousins, D. J., Durham, S. R., & Till, S. J. (2017). Intradermal grass pollen immunotherapy increases T_H2 and IgE responses and worsens respiratory allergic symptoms. Journal of Allergy and Clinical Immunology, 139(6), 1830-1839. https://doi.org/10.1016/j.jaci.2016.09.024

@article{204cfc4198c24e0c93a9d61be1a4f981,

title = "Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms",

abstract = "Background: Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy. Objective: We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. Methods: We randomly assigned 93 adults with grass pollen-induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment. Results: There was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, -172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, -11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense-specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03). Conclusion: Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.",

keywords = "Allergy immunotherapy, allergic rhinitis, grass pollen, Phleum Pratense, immunotherapy, intradermal, low-dose",

author = "Anna Slovick and Abdel Douiri and Rachel Muir and Andrea Guerra and Konstantinos Tsioulos and Evie Hay and Lam, {Emily P.S.} and Joanna Kelly and Peacock, {Janet L.} and Ying Sun and Shamji, {Mohamed H.} and Cousins, {David J.} and Durham, {Stephen R.} and Till, {Stephen J.}",

year = "2017",

month = jun,

doi = "10.1016/j.jaci.2016.09.024",

language = "English",

volume = "139",

pages = "1830--1839",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "MOSBY, INC",

number = "6",

}

Slovick, A , Douiri, A , Muir, R , Guerra, A , Tsioulos, K, Hay, E, Lam, EPS , Kelly, J , Peacock, JL , Sun, Y, Shamji, MH, Cousins, DJ, Durham, SR & Till, SJ 2017, 'Intradermal grass pollen immunotherapy increases T_H2 and IgE responses and worsens respiratory allergic symptoms', Journal of Allergy and Clinical Immunology, vol. 139, no. 6, pp. 1830-1839. https://doi.org/10.1016/j.jaci.2016.09.024

TY - JOUR

T1 - Intradermal grass pollen immunotherapy increases TH2 and IgE responses and worsens respiratory allergic symptoms

AU - Slovick, Anna

AU - Douiri, Abdel

AU - Muir, Rachel

AU - Guerra, Andrea

AU - Tsioulos, Konstantinos

AU - Hay, Evie

AU - Lam, Emily P.S.

AU - Kelly, Joanna

AU - Peacock, Janet L.

AU - Sun, Ying

AU - Shamji, Mohamed H.

AU - Cousins, David J.

AU - Durham, Stephen R.

AU - Till, Stephen J.

PY - 2017/6

Y1 - 2017/6

N2 - Background: Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy. Objective: We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. Methods: We randomly assigned 93 adults with grass pollen-induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment. Results: There was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, -172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, -11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense-specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03). Conclusion: Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.

AB - Background: Repeated low-dose grass pollen intradermal allergen injection suppresses allergen-induced cutaneous late-phase responses comparably with conventional subcutaneous and sublingual immunotherapy. Objective: We sought to evaluate the efficacy and safety of grass pollen intradermal immunotherapy in the treatment of allergic rhinitis. Methods: We randomly assigned 93 adults with grass pollen-induced allergic rhinitis to receive 7 preseasonal intradermal allergen injections (containing 7 ng of Phl p 5 major allergen) or a histamine control. The primary end point was daily combined symptom-medication scores during the 2013 pollen season (area under the curve). Analysis was by intention to treat. Skin biopsy specimens were collected after intradermal allergen challenges, and late-phase responses were measured 4 and 7, 10, or 13 months after treatment. Results: There was no significant difference in the primary end point between treatment arms (active, n = 46; control, n = 47; median difference, 14; 95% CI, -172.5 to 215.1; P = .80). Among secondary end points, nasal symptoms were worse in the intradermal treatment group, as measured based on daily (median difference, 35; 95% CI, 4.0-67.5; P = .03) and visual analog scale (median difference, 53; 95% CI, -11.6 to 125.2; P = .05) scores. In a per-protocol analysis intradermal immunotherapy was further associated with worse asthma symptoms and fewer symptom-free days. Intradermal immunotherapy increased serum Phleum pratense-specific IgE levels (P = .001) compared with those in the control arm. T cells cultured from biopsy specimens of subjects undergoing intradermal immunotherapy had higher expression of the TH2 surface marker CRTH2 (P = .04) and lower expression of the TH1 marker CXCR3 (P = .01), respectively. Late-phase responses remained inhibited 7 months after treatment (P = .03). Conclusion: Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.

KW - Allergy immunotherapy

KW - allergic rhinitis

KW - grass pollen

KW - Phleum Pratense

KW - immunotherapy

KW - intradermal

KW - low-dose

UR - http://www.scopus.com/inward/record.url?scp=85007251464&partnerID=8YFLogxK

U2 - 10.1016/j.jaci.2016.09.024

DO - 10.1016/j.jaci.2016.09.024

M3 - Article

SN - 0091-6749

VL - 139

SP - 1830

EP - 1839

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 6

ER -

Intradermal grass pollen immunotherapy increases T_H2 and IgE responses and worsens respiratory allergic symptoms

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