Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3‐expressing cells and elevated allergen‐specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E‐facilitated allergen binding to B cells

Abstract

SummaryBackground The mechanisms of sublingual immunotherapy (SLIT) are less well understood than those of subcutaneous immunotherapy (SCIT). Objectives To determine the effects of grass-pollen SLIT on oral mucosal immune cells, local regulatory cytokines, serum allergen-specific antibody subclasses and B cell IgE-facilitated allergen binding (IgE-FAB). Methods Biopsies from the sublingual mucosa of up to 14 SLIT-treated atopics, nine placebotreated atopics and eight normal controls were examined for myeloid dendritic cells (mDCs) (CD1c), plasmacytoid dendritic cells (CD303), mast cells (AA1), T cells (CD3) and Foxp3 using immunofluorescence microscopy. IL-10 and TGF-b mRNA expression were identified by in situ hybridization. Allergen-specific IgG and IgA subclasses and serum inhibitory activity for binding of allergen-IgE complexes to B cells (IgE-FAB) were measured before, during and on the completion of SLIT. Results Foxp31 cells were increased in the oral epithelium of SLIT-vs. placebo-treated atopics (P = 0.04). Greater numbers of subepithelial mDCs were present in placebo-treated, but not in SLIT-treated, atopics compared with normal controls (P = 0.05). There were fewer subepithelial mast cells and greater epithelial T cells in SLIT-compared with placebo-treated atopics (P = 0.1 for both). IgG 1 and IgG 4 were increased following SLIT (Po0.001). Peak seasonal IgA 1 and IgA 2 were increased during SLIT (Po0.05). There was a time-dependent increase in serum inhibitory activity for IgE-FAB in SLIT-treated atopics.Conclusions SLIT with grass pollen extract is associated with increased Foxp3 1 cells in the sublingual epithelium and systemic humoral changes as observed previously for SCIT.

Oral myeloid cells uptake allergoids coupled to mannan driving Th1/Treg responses upon sublingual delivery in mice

“…The preferential regional induction of Treg cells by the sublingual administration fits with the description of an increase in Treg cells in the sublingual mucosa in patients receiving SLIT 40. These cells may migrate from regional lymphoid organs or induced within the oral mucosa through local DC‐T cell interaction 40. Interestingly, an increase in Treg cells in submandibular LNs following SLIT has been described with antigen formulations that presumably facilitates the allergen capture by oral DCs 13, 27.…”

“…In this sense, the sublingual route seems less effective than the subcutaneous to induce these cells systemically (ie, in the spleen), as by s.c. injection, the increase in Treg cells was readily detectable in the spleen after just 3 doses/4 weeks with the same PM‐allergoids used here 16. The preferential regional induction of Treg cells by the sublingual administration fits with the description of an increase in Treg cells in the sublingual mucosa in patients receiving SLIT 40. These cells may migrate from regional lymphoid organs or induced within the oral mucosa through local DC‐T cell interaction 40.…”

“…It has been suggested that an ideal allergen vaccine would target DCs, yet not be recognized by mast cell surface IgE 40. Mastocytes are abundant in the sublingual mucosa, and their activation through IgE is thought to account for the frequent local side effects during SLIT 40, 42.…”

“…Mastocytes are abundant in the sublingual mucosa, and their activation through IgE is thought to account for the frequent local side effects during SLIT 40, 42. In this sense, PM‐allergoids have the advantage over the native allergens that show a very limited reactivity with specific IgE 16, 17, 18 and very low ability to activate skin mastocytes or blood basophils from sensitized patients 16.…”

Diagnosis and treatment of allergic diseases in Zhejiang Province: A cross-sectional survey

“…SCIT is a conventional treatment, which has more than 100 years of history with proved efficacy (Ring and Gutermuth, 2011). SLIT is a relatively new treatment that started in 1986, however with comparable immunologic mechanisms (Scadding et al, 2010;James et al, 2011). The potential side effects of anaphylaxis in SCIT largely restricted its clinical application, mainly because of the concerns about its safety raised by patients as well as doctors.…”