Distinct modulation of allergic T cell responses by subcutaneous vs. sublingual allergen-specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy is the only curative treatment for type I allergy. It can be administered subcutaneously (SCIT) or sublingually (SLIT). The clinical efficacy of these two treatment modalities appears to be similar, but potential differences in the immunological mechanisms involved have not been fully explored. OBJECTIVE: To compare changes in the allergen-specific T cell response induced by subcutaneous vs. sublingual administration of allergen-specific immunotherapy (AIT). METHODS: Grass pollen-allergic patients were randomized into groups receiving either SCIT injections or SLIT tablets or neither. PBMCs were tested for Timothy grass (TG)-specific cytokine production by ELISPOT after in vitro expansion with TG-peptide pools. Phenotypic characterization of cytokine-producing cells was performed by FACS. RESULTS: In the SCIT group, decreased IL-5 production was observed starting 10 months after treatment commenced. At 24 months, T cell responses showed IL-5 levels significantly below the before-treatment baseline. No significant reduction of IL-5 was observed in the SLIT or untreated group. However, a significant transient increase in IL-10 production after 10 months of treatment compared to baseline was detected in both treatment groups. FACS analysis revealed that IL-10 production was associated with CD4(+) T cells that also produced IFNγ and therefore may be associated with an IL-10-secreting type 1 cell phenotype. CONCLUSION AND CLINICAL RELEVANCE: The most dominant immunological changes on a cellular level were a decrease in IL-5 in the SCIT group and a significant, transient increase of IL-10 observed after 10 months of treatment in both treated groups. The distinct routes of AIT administration may induce different immunomodulatory mechanisms at the cellular level.

Immunological comparison of allergen immunotherapy tablet treatment and subcutaneous immunotherapy against grass allergy.

BACKGROUND: IgE-mediated allergic rhinitis to grass pollen can successfully be treated with either allergen immunotherapy tablets (SLIT tablet) or SQ-standardized subcutaneous immunotherapy (SCIT). The efficacy of these two treatment modalities for grass allergy is comparable, but the immunological mechanisms may differ. ClinicalTrials.gov ID: NCT01889875. OBJECTIVES: To compare the immunological changes induced by SQ-standardized SCIT and SLIT tablet. METHODS: We randomized 40 individuals with grass pollen rhinitis into groups receiving SCIT, SLIT tablet, or neither and followed them for 15 months with regular serum measurements of specific IgE, IgG4, IgE-blocking factor, facilitated antigen presentation (FAP), and basophil activation test (BAT). Nasal challenges were used to assess changes in nasal sensitivity. RESULTS: After 15 months of treatment IgG4, IgE-blocking factor, FAP, and BAT values differed significantly in both SCIT and SLIT-tablet treatment groups when compared to the control group. Both SCIT and SLIT-tablet groups were significantly different from the control group after 1­3 months of treatment. In general, the changes induced by SCIT reached twice that of SLIT tablet, with the exception of specific IgE where SLIT tablet induced initial threefold increase compared with SCIT. A slight but significant increase in IgE and BAT after season was seen only in the control group. Significant differences between SCIT and SLIT tablet were observed early, but the differences diminished with the length of treatment, especially for FAP inhibition. CONCLUSIONS: Both SCIT and SLIT tablet induce significant changes in specific antibodies (IgE and IgG4) and competition assays (IgE-blocking factor, FAP, and BAT). Overall, SCIT induced larger (two- to threefold) changes than SLIT tablet, with the exception of FAP, where SLIT tablet showed a gradual increase ending at the same level as SCIT. Maximal change was generally reached after 3 months' treatment.

Specific immunotherapy can greatly reduce the need for systemic steroids in allergic rhinitis.

BACKGROUND: Worldwide, more than 400 million individuals have allergic rhinitis, which has a significant impact on the individual's general health. Most patients self-medicate with over-the-counter drugs, but severe cases need treatment with topical corticosteroids and/or immunotherapy (SCIT). Although the ARIA guidelines discourage the use of systemic corticosteroids, this treatment is often used by general practitioners. AIMS: To investigate the use of systemic steroids to treat allergic rhinitis in Denmark and the role of SCIT as an alternative. METHODS: A retrospective study based on Danish National Registry databases 1995-2009. Steroid use was defined as a minimum of one steroid injection during April-July for at least three consecutive years. SCIT treatment against grass (Phleum pratense), birch (Betula verrucosa) or both was included. RESULTS: Overall, 39 173 individuals were treated with either SCIT or steroids; 93.1% received only steroids, and 6.9% received SCIT and/or steroids. The steroid-to-SCIT ratio was 14 : 1 (P < 0.0001). The mean annual steroid injections were 1.6 in the steroid-only group and 1.0 in the SCIT group (P < 0.0001). Of the SCIT-treated individuals, 84% did not need steroids after SCIT treatment (P < 0.0001). The hazard ratios of receiving steroids after SCIT against grass, birch or both were 0.65, 0.83 and 0.72, respectively (P < 0.0001), when compared with the steroids-only group. The maximum hazard reduction was obtained if patients responded well to SCIT treatment after one to 3 years. CONCLUSIONS: Systemic steroid injections are still widely used to treat pollen allergy. Specific immunotherapy can greatly reduce the need for steroids.