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).
  
  
  CONCLUSIONS
  Intradermal allergen immunotherapy suppressed skin late-phase responses but was not clinically effective and resulted in worsening of respiratory allergic symptoms.
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom; MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, London, United Kingdom.
authors: Anna
authors: A
authors: Slovick
authors: Division of Health and Social Care Research, King's College London, 4th floor Addison House, Guy's Campus, London, United Kingdom.
authors: Abdel
authors: A
authors: Douiri
authors: Clinical Research Facility, NIHR Biomedical Research Centre, Guy's Hospital, London, United Kingdom.
authors: Rachel
authors: R
authors: Muir
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom.
authors: Andrea
authors: A
authors: Guerra
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom.
authors: Konstantinos
authors: K
authors: Tsioulos
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom.
authors: Evie
authors: E
authors: Hay
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom.
authors: Emily P S
authors: EPS
authors: Lam
authors: King's Clinical Trials Unit, King's College London, Institute of Psychiatry, London, United Kingdom.
authors: Joanna
authors: J
authors: Kelly
authors: Division of Health and Social Care Research, King's College London, 4th floor Addison House, Guy's Campus, London, United Kingdom.
authors: Janet L
authors: JL
authors: Peacock
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom.
authors: Sun
authors: S
authors: Ying
authors: Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, United Kingdom.
authors: Mohamed H
authors: MH
authors: Shamji
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom; Department of Infection, Immunity and Inflammation, NIHR Leicester Respiratory Biomedical Research Unit, Leicester Institute for Lung Health, University of Leicester, Leicester, United Kingdom; MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, London, United Kingdom.
authors: David J
authors: DJ
authors: Cousins
authors: Allergy and Clinical Immunology, National Heart and Lung Institute, Faculty of Medicine, Imperial College, London, United Kingdom.
authors: Stephen R
authors: SR
authors: Durham
authors: Division of Asthma, Allergy and Lung Biology, King's College London, School of Medicine, Guy's Hospital, London, United Kingdom; MRC-Asthma UK Centre for Allergic Mechanisms of Asthma, London, United Kingdom. Electronic address: stephen.till@kcl.ac.uk.
authors: Stephen J
authors: SJ
authors: Till
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007271:Injections, Intradermal; D008297:Male; D008875:Middle Aged; D031784:Phleum / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D006255:Rhinitis, Allergic, Seasonal / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012867:Skin / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000485:Allergens; D007073:Immunoglobulin E
keywords: Allergy immunotherapy; Phleum pratense; allergic rhinitis; grass pollen; immunotherapy; intradermal; low dose