Evaluation of recombinant and native timothy pollen (rPhl p 1, 2, 5, 6, 7, 11, 12 and nPhl p 4)- specific IgG4 antibodies induced by subcutaneous immunotherapy with timothy pollen extract in allergic patients

Int Arch Allergy Immunol. 2004 Sep;135(1):44-53. doi: 10.1159/000080042. Epub 2004 Jul 30.


Background: Allergen immunotherapy is a widely accepted treatment for IgE-mediated allergies. The evaluation of immunotherapy-induced IgG4 antibodies based on allergen extract is questionable because the amount of allergen-extract-specific IgG4 to individual disease-eliciting allergens cannot be determined using crude allergen extracts. In this study, we examined the specific IgE and IgG4 serum binding profiles to individual Phleum pratense allergens in grass-pollen-sensitive patients who had received grass-pollen-specific immunotherapy (SIT).

Methods: The study included 33 patients from North-West Italy. All suffered from seasonal rhinoconjunctivitis and/or asthma. A modified "cluster" regimen of injections of a standardized aluminium-adsorbed P.pratense extract, with once-weekly visits and 10 injections for 5 weeks followed by 3 weeks of maintenance injections was instituted. Patients' sera were analyzed for specific IgE and IgG4 reactivity to individual P. pratense allergens (recombinant Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 11, Phl p12 and native Phl p 4) and natural P. pratense extract using the Pharmacia CAP system.

Results: IgE reactivities to new allergen components were not detected by CAP in treated patients after 15 weeks and a cumulative dose of approximately 65 microg of the major allergen Phl p 5. Patients lacking specific IgE reactivity towards individual allergens at the start of SIT did not produce significant levels of specific serum IgG4 to serum IgE-negative allergens. On the other hand, an increase in specific IgG4 only to allergens to which patients were previously sensitized was observed. Significant increases in specific IgG4 levels to rPhl p 1 (p < 0.05), 2 (p < (0.01), 5 (p < 0.0001), 6 (p < 0.0001), 7 (p < 0.05), 11 (p < 0.05) and nPhl p 4 (p < 0.01) were observed after P. pratense extract immunotherapy. No significant rPhl p 12-specific IgG4 antibody increase was documented after treatment.

Conclusion: These findings suggest that Phl p 12 was underrepresented in the extract used, as indicated by the low specific IgG4 response induced by this grass-pollen-specific vaccine. Thus, the simple detection of specific serum IgG4 antibodies a few weeks after the start of SIT could represent a valuable tool to estimate the presence of relevant allergens in a given immunotherapeutic allergen extract.

MeSH terms

  • Adolescent
  • Adult
  • Allergens / chemistry
  • Allergens / immunology*
  • Asthma / immunology
  • Asthma / therapy
  • Child
  • Conjunctivitis, Allergic / immunology
  • Conjunctivitis, Allergic / therapy
  • Desensitization, Immunologic / methods
  • Female
  • Humans
  • Hypersensitivity / immunology*
  • Hypersensitivity / therapy
  • Immunoglobulin E / immunology
  • Immunoglobulin G / immunology*
  • Male
  • Middle Aged
  • Phleum / chemistry
  • Phleum / immunology*
  • Plant Extracts / chemistry
  • Plant Extracts / immunology
  • Pollen / chemistry
  • Pollen / immunology*
  • Rhinitis, Allergic, Seasonal / immunology
  • Rhinitis, Allergic, Seasonal / therapy


  • Allergens
  • Immunoglobulin G
  • Plant Extracts
  • Immunoglobulin E