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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Citations (Scopus)
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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.

Original languageEnglish
Pages (from-to)1830-1839
Number of pages10
JournalJournal of Allergy and Clinical Immunology
Issue number6
Early online date20 Oct 2016
Publication statusPublished - Jun 2017


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


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