Subcutaneous Versus Sublingual Immunotherapy for Allergic Rhinitis and/or Asthma

Nerin Nadir Bahceciler; Nazan Cobanoglu

Disclosures

Immunotherapy. 2011;3(6):747-756. 

In This Article

Antibody Responses

Successful SCIT may involve blunting of the seasonal increase in serum pollen allergen-specific IgE concentrations[82] in addition to substantial increases in allergen-specific IgG4.[73,82,83] The increase in the ratio of specific IgG4:specific IgE may be crucial. Recent studies have confirmed elevations in allergen-specific IgA after SCIT.[73,84] It is possible to measure the functional activity of these antibodies. IgG4 is noninflammatory since it is unable to fix complement and does not form immune complexes. B cells are able to take up allergen bound to IgE via the surface receptor CD23. They subsequently process this allergen and present epitopes to T cells. This results in effective T-cell activation at low concentrations of allergen. Complexes bound to CD23 on the surface of B cells can be quantified by flow cytometry. Serum obtained from subjects with hayfever after successful immunotherapy has been shown to inhibit allergen–IgE binding to B cells,[82] with the effect mediated by IgG4. This system has provided an in vitro assay of the efficacy of 'blocking' antibodies induced by immunotherapy.

The immunologic response to SLIT has not been intensely studied. A previous study reported changes in specific IgG4 levels,[69] whereas others reported a lack of change in specific IgG4[85] and IgE levels.[71] Moreover, in some SLIT studies, investigators observed a decrease in the IgE:IgG4 ratio.[72] A recent report of HDM-SLIT of asthmatic children demonstrated the downregulation of specific IgE in serum in combination with slight upregulation of specific IgA, but with no effect on IgG1 and IgG4.[72] Two recent, large-scale, DBPC studies demonstrated dose-dependent specific antibody changes during grass pollen SLIT.[40,41] Durham et al. enrolled 855 individuals with seasonal allergic rhinitis from Europe and Canada.[40] Placebo or one of three different doses of grass allergen (Timothy grass) tablet; 2500, 25,000 and 75,000 SQ-T (corresponding to 0.5, 5 and 15 µg of the major allergen Phleum p 5) were administered daily. Administration began from approximately 8 weeks before the start of the grass pollen season and was continued for a total of 18 weeks. Specific IgG levels were raised at 8 weeks in the highest-dose group and continued to increase, along with levels in the intermediate-dose group, up to 18 weeks post-treatment. Conversely, levels of specific IgE peaked at 8 weeks and remained elevated post-treatment, but without further seasonal rise. By contrast, placebo-treated patients showed no early changes in specific IgG but significant seasonal increase in specific IgE.

Didier et al. performed a similar international PC trial in 628 adults with seasonal allergic rhinitis.[41] A sublingual tablet consisting of equal amounts of allergen extracts from five different grasses was used, as opposed to Timothy grass alone. Levels of grass pollen-specific IgG4 were increased relative to placebo in a dose-dependent manner. Increases were in the region of three-times those seen at baseline – broadly similar to those demonstrated in the study by Durham et al..[40] Specific IgE levels increased only in the treatment groups. These trials show a clear relationship between dose, efficacy and specific antibody levels.

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