Lack of Detectable Alterations in Immune Responses during Sublingual Immunotherapy in Children with Seasonal Allergic Rhinoconjunctivitis to Grass Pollen

Abstract

BACKGROUND: Recent work indicates that subcutaneous specific immunotherapy induces specific T-cell anergy, a shift in the TH1/TH2 ratio, and antibody production in favor of IgG4. There are few data on sublingual immunotherapy (SLIT), especially in children. METHODS: We assessed the proliferation of peripheral blood mononuclear cells ((3)H-thymidine incorporation) and secretion of interleukin (IL)-4, interferon (IFN)gamma and IL-5 (ELISA) after in vitro stimulation with allergen or phytohemagglutinin (PHA) in 29 children with allergic rhinoconjunctivitis receiving SLIT with grass pollen before, and after 1 and 2 years of treatment in a multicenter placebo-controlled study on the efficacy of the treatment. Further, non-specific intracellular production of IL-4, IL-13, IFNgamma, IL-2, IL-10 and IL-5 (FACS) and serum total and specific IgE and IgG4 (ELISA) were analyzed. RESULTS: Proliferation and IL-4 and IL-5 secretion after stimulation with allergen or PHA did not differ between the groups. In addition, we observed no effect of SLIT on intracellular cytokine production. IFNgamma secretion after allergen coculture was comparable between the groups. Following PHA stimulation, IFNgamma secretion was significantly higher in the SLIT group after 1 year, and a trend was observable already before and after 2 years of treatment, probably due to the inhomogeneity in the groups despite randomization (for age and asthma). No significant changes were observed for sIgE/sIgG4 ratios over time either in or between the groups. CONCLUSION: During 2 years of SLIT in children with a positive effect on rescue medication use, we observed no significant effects on in vitro T-cell immune responses or immunoglobulins. So far, pediatric studies demonstrating stable effects of SLIT on such reactions are missing, probably due to limited effects of SLIT on systemic immunologic reactions.