title: The Impact on Allergy-Related Cells of a Birch Pollen Allergoid, with and without Monophosphoryl Lipid A, in Comparison with the Native Equivalent.
abstract: BACKGROUND
  The clinical efficacy and safety of allergoid immunotherapy have been demonstrated in clinical trials. However, simultaneous monitoring of the immunological changes by allergoids versus allergens in the cells of the same individual has not been extensively performed, and the impact of concurrent Toll-like receptor 4 (TLR4) ligation has not been specified.
  
  
  METHODS
  Three types of birch allergen were utilized: glutaraldehyde-treated allergoid (extract A), the same allergoid plus monophosphoryl lipid A (MPL), i.e., TLR4 ligand (extract A*), and native allergen (extract B). Antigen-specific responses after the in vitro stimulation of blood cells with the extracts were assessed by studying costimulatory receptors on the B cell surface by flow cytometry, cytokine responses by ELISA, and CD63 and CD203c upregulation (basophil activation test) in allergic versus nonallergic subjects.
  
  
  RESULTS
  HLA-DR selectively increased upon allergen or allergoid treatment in the allergic group only. The extract types elicited similar cytokine responses, with IL-6 and IL-10 production detected only in certain atopic subjects. The allergoids revealed a strong reduction (100- to <10,000-fold) in basophil activation versus native allergen. Reactivity was undetectable in the basophils from nonallergic subjects.
  
  
  CONCLUSIONS
  The allergenicity of the allergoid employed was sharply reduced when compared to the native allergen, while its immunogenicity was largely retained, especially in the presence of MPL. We also provide further evidence that allergic and nonallergic individuals show preexisting differences in their immune repertoires.
authors.affiliation: Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
authors.forename: Dennis
authors.initials: D
authors.lastname: Ernst
authors.forename: Markus
authors.initials: M
authors.lastname: Kraller
authors.forename: Magda
authors.initials: M
authors.lastname: Babina
mesh_terms: D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000485:Allergens / Q000276:immunology*; D000080384:Allergoids; D001491:Basophils / Q000276:immunology; D029662:Betula / Q000276:immunology*; D002478:Cells, Cultured; D003888:Desensitization, Immunologic / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use; D010727:Phosphoric Diester Hydrolases / Q000096:biosynthesis; D010936:Plant Extracts / Q000276:immunology*; D011058:Pollen / Q000276:immunology*; D011755:Pyrophosphatases / Q000096:biosynthesis; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology*; D060149:Tetraspanin 30 / Q000096:biosynthesis; D051197:Toll-Like Receptor 4 / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000485:Allergens; D000080384:Allergoids; C554586:CD63 protein, human; C427944:ENPP3 protein, human; D006684:HLA-DR Antigens; C508609:IL10 protein, human; C508600:IL6 protein, human; D015850:Interleukin-6; D008050:Lipid A; D010936:Plant Extracts; C495345:TLR4 protein, human; D060149:Tetraspanin 30; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; C048436:monophosphoryl lipid A