title: Pretreatment IgE sensitization patterns determine the molecular profile of the IgG4 response during updosing of subcutaneous immunotherapy with timothy grass pollen extract.
abstract: Allergen immunotherapy is an effective treatment of allergic rhinoconjunctivitis. Clinical efficacy is associated with improvement of basophil sensitivity and an increase in allergen-specific immunoglobulin concentration.
  
  
  
  We sought to determine whether changes in allergen component-specific serum IgE and IgG4 levels during the updosing phase of subcutaneous immunotherapy (SCIT) are biomarkers of the immunologic changes that can lead to treatment efficacy.
  
  
  
  Twenty-four subjects with grass pollen-induced allergic rhinoconjunctivitis were randomized 3:1 to receive SCIT (Alutard SQ) or to an open control group. IgE and IgG4 concentrations were determined for the major allergens Phl p 1 or Phl p 5 by using ImmunoCAP and for 8 grass pollen molecules by using Immuno Solid-phase Allergy Chip (ISAC) before treatment and after updosing.
  
  
  
  Levels of specific IgE against the dominant major allergens Phl p 1 and Phl p 5 increased from a mean of 23.0 to 48.8 kU/L (P = .01, n = 18) during the updosing phase in ImmunoCAP measurements but decreased from a median of 4.6 ISAC specific units (ISU) to 2.14 ISU (P < .0001, n = 102) when measured by using ISAC against 8 grass allergen components. The updosing phase induced a specific IgG4 level increase from a median of 0 ISU before treatment to 0.83 ISU after 12 weeks (P < .0001, n = 102) but only for allergen molecules to which pretreatment-specific IgE antibodies were detected (Spearman σ = 0.72, P < .0001, n = 102).
  
  
  
  Pretreatment allergen component-specific IgE appears to determine the induction of IgG4 in the updosing phase. Induced IgG4 seems to suppress IgE levels on ISAC, resulting in a marked decrease in ISAC-measured specific IgE levels after updosing of SCIT. Thus this decrease in ISAC IgE levels can be used to monitor the blocking effect of allergen-specific immunotherapy-induced non-IgE antibodies.
authors.affiliation: Departments of Respiratory Medicine and Allergy, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Johannes Martin
authors.initials: JM
authors.lastname: Schmid
authors.affiliation: Global Research, ALK-Abelló, Hørsholm, Denmark.
authors.forename: Peter Adler
authors.initials: PA
authors.lastname: Würtzen
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Ronald
authors.initials: R
authors.lastname: Dahl
authors.affiliation: Departments of Respiratory Medicine and Allergy, Aarhus University Hospital, Aarhus, Denmark. Electronic address: hjh@clin.au.dk.
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Hoffmann
mesh_terms: D000485:Allergens / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D015415:Biomarkers; D003888:Desensitization, Immunologic / Q000379:methods; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007279:Injections, Subcutaneous; D008297:Male; D031784:Phleum / Q000009:adverse effects* / Q000276:immunology; D010936:Plant Extracts / Q000009:adverse effects / Q000276:immunology; D011058:Pollen / Q000276:immunology*; D015203:Reproducibility of Results; D006255:Rhinitis, Allergic, Seasonal / Q000175:diagnosis / Q000276:immunology* / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D015415:Biomarkers; D007074:Immunoglobulin G; D010936:Plant Extracts; D007073:Immunoglobulin E
keywords: Grass pollen allergy; allergen component–specific IgE; allergen component–specific IgG(4); allergen immunotherapy biomarker; component-resolved diagnosis; molecular allergy; subcutaneous immunotherapy