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 (³H-thymidine incorporation) and secretion of interleukin (IL)-4, interferon (IFN)γ 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, IFNγ, 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. IFNγ secretion after allergen coculture was comparable between the groups. Following PHA stimulation, IFNγ 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.

Early Cytokine Modulation after the Rapid Induction Phase of Sublingual Immunotherapy with Mite Monomeric Allergoids

“…A recent study demonstrated that SLIT for birch pollen was able to induce IL-l a production during the early phase of treatment (9). On the contrary, other authors did not observe any significant changes in cytokine production (IL-lO, IFN-y, IL-4, TGF-P) in allergen-stimulated cultures during the early phase of treatment (13)(14). These different results may be partially explained by the different cell culture protocols applied in the various studies and by the different commercial products utilized.…”

“…The present work was designed to evaluate whether also with SLIT, a rapid dose build-up phase of treatment could induce a more rapid modulation of the immune system than the traditional induction schedule (13)(14). The study included twenty patients allergic to Dermatophagoides pteronyssinus (Dp).…”

Low-Dose IL-2 Induces Regulatory T Cell–Mediated Control of Experimental Food Allergy

“…A switch to Th1 immune responses was already reported in AIT (35), including in food allergy treatment (36). Even though Th1 redirection induced by AIT with allergen extracts or peptides continues to be reported in more recent publications (37,38), other groups, however, did not observe this effect (39). More recently, the induction of allergen-specific Tregs producing IL-10 has been considered as a main event causing peripheral T cell tolerance (35).…”

Allergen immunotherapy for allergic respiratory diseases

“…120,121 Other studies of SLIT observed a suppression of T cells proliferative responses, elevated level of INF-gamma and a reduction in Th2 cytokines [122][123][124][125][126] whereas some studies did not confirm this last finding in peripheral blood cells. [127][128][129] Other immunological changes in peripheral blood mononuclear cells from SLIT treated patients include increased expression of the programmed cell death ligand (PD-L1) on B cells and monocytes. 130 A significant reduction in the number of eosinophils and neutrophils in the nasal mucosa 131 has been reported.…”