title: Preventive sublingual immunotherapy in preschool children: first evidence for safety and pro-tolerogenic effects.
abstract: BACKGROUND
  Prevention of new IgE sensitizations has been described during allergen-specific immunotherapy. However, prospective data using a preventive approach in very young children who would benefit most are missing. We initiated a prospective pilot study investigating the safety, immunomodulatory, and sensitization-preventive effect of sublingual immunotherapy (SLIT) in mono/oligoclonally sensitized, clinically asymptomatic children 2-5 yr of age.
  
  
  METHODS
  In this double-blinded, randomized, placebo-controlled pilot study, 31 mono-/oligosensitized children to house-dust mite or grass pollen were included. SLIT with the respective source (n = 15) or placebo (n = 16) was applied. After dose-up-phase therapy was continued for 2 yr. Parents recorded clinical events, vaccinations, and drug intake in a diary. Skin prick testing and specific IgE and IgG measurements were recorded at baseline, 12 and 24 months. At the same time, allergen-specific proliferation and IL10- and TGFβ-dependent Treg function were measured.
  
  
  RESULTS
  Preventive application of SLIT in young children was safe (no relevant side effects in 21,170 single applications). After 12 and 24 months of treatment, the rate of allergen-specific sensitization (specific IgE and SPT reactivity) was comparable in the treatment and the placebo group. However, verum-treated patients displayed a significant up-regulation of allergen-specific IgG (p < 0.05). Furthermore, IL10-dependent inhibition (p < 0.05) was observed in vitro in the treatment group but not in the placebo group.
  
  
  CONCLUSIONS
  Preventive SLIT is safe in children 2-5 yr of age and induces regulatory mechanisms involving allergen-specific IgG and IL10. Based on this pilot study, large-scale trials will need to investigate the modulation of sensitization and clinically relevant allergy.
authors.affiliation: Department of Paediatrics, Medical University of Vienna, Vienna, Austria.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Szépfalusi
authors.forename: Christina
authors.initials: C
authors.lastname: Bannert
authors.forename: Leila
authors.initials: L
authors.lastname: Ronceray
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Mayer
authors.forename: Michaela
authors.initials: M
authors.lastname: Hassler
authors.forename: Eva
authors.initials: E
authors.lastname: Wissmann
authors.forename: Eleonora
authors.initials: E
authors.lastname: Dehlink
authors.forename: Saskia
authors.initials: S
authors.lastname: Gruber
authors.forename: Alexandra
authors.initials: A
authors.lastname: Graf
authors.forename: Christian
authors.initials: C
authors.lastname: Lupinek
authors.forename: Rudolf
authors.initials: R
authors.lastname: Valenta
authors.forename: Thomas
authors.initials: T
authors.lastname: Eiwegger
authors.forename: Radvan
authors.initials: R
authors.lastname: Urbanek
mesh_terms: D000286:Administration, Sublingual; D000485:Allergens / Q000276:immunology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology; D058070:Asymptomatic Diseases; D049109:Cell Proliferation; D002478:Cells, Cultured; D002675:Child, Preschool; D003888:Desensitization, Immunologic / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007108:Immune Tolerance; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000378:metabolism; D008213:Lymphocyte Activation; D008297:Male; D010865:Pilot Projects; D010919:Placebos; D006109:Poaceae; D011058:Pollen / Q000276:immunology; D011446:Prospective Studies; D039981:Pyroglyphidae; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000485:Allergens; D039741:Antigens, Dermatophagoides; D007074:Immunoglobulin G; D010919:Placebos; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007073:Immunoglobulin E
keywords: IgE sensitization; allergen-specific immunotherapy; allergy prevention; skin prick test; specific IgE