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

J Allergy Clin Immunol. 2017 Jun;139(6):1830-1839.e13. doi: 10.1016/j.jaci.2016.09.024. Epub 2016 Oct 20.

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; Phleum pratense; allergic rhinitis; grass pollen; immunotherapy; intradermal; low dose.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Allergens / administration & dosage*
  • Allergens / immunology
  • Desensitization, Immunologic / methods*
  • Double-Blind Method
  • Female
  • Humans
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology
  • Injections, Intradermal
  • Male
  • Middle Aged
  • Phleum / immunology*
  • Pollen / immunology*
  • Rhinitis, Allergic, Seasonal / blood
  • Rhinitis, Allergic, Seasonal / immunology
  • Rhinitis, Allergic, Seasonal / pathology
  • Rhinitis, Allergic, Seasonal / therapy*
  • Skin / pathology
  • Th2 Cells / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • Allergens
  • Immunoglobulin E