Abstract

BACKGROUND
Allergen-specific immunotherapy is the only mode of therapy that has been demonstrated to offer a cure in patients with IgE-mediated respiratory allergies.
OBJECTIVE
We sought to demonstrate the safety and efficacy of timothy grass (TG) and dust mite (DM) dual sublingual immunotherapy (SLIT) and to begin to investigate the immune mechanisms involved in successful immunotherapy with multiple allergens.
METHODS
The safety and efficacy of dual SLIT with TG and DM in children and adults with demonstrated allergies to TG and DM were investigated in a single-center, randomized, double-blind, controlled phase I study. Thirty subjects received either TG and DM dual SLIT (n= 20) or placebo (n = 10). Immune parameters were evaluated for differentiation of desensitized subjects from control subjects.
RESULTS
Subjects treated with dual SLIT had decreased rhinoconjunctivitis scores (P < .001) and medication use scores (P < .001) and reduced responses to TG and DM allergen based on results of skin prick tests or nasal disk challenges (P < .01 and P < .001, respectively) compared with placebo-treated control subjects. An increase in TG- and DM-specific IgG(4) levels, reduced allergen-specific IgE levels, and subsequent basophil activation were observed in the active treatment group. Dual SLIT promoted allergen-specific suppressive CD4(+)CD25(high)CD127(low)CD45RO(+) forkhead box protein 3 (Foxp3)(+) memory regulatory T cells with reduced DNA methylation of CpG sites within the Foxp3 locus.
CONCLUSION
The results of this pilot study suggest that dual SLIT could be an effective means to treat subjects with sensitivities to a variety of allergens and that long-term tolerance might be induced by epigenetic modifications of Foxp3 in memory regulatory T cells.

Links

Publisher Full Text

Authors

Swamy RS, Reshamwala N, Hunter T, Vissamsetti S, Santos CB, Baroody FM, Hwang PH, Hoyte EG, Garcia MA, Nadeau KC

Institution

Division of Immunology and Allergy, Stanford University, Stanford, CA 94305-5208, USA

Source

The Journal of allergy and clinical immunology 130:1 2012 Jul pg 215-24.e7

MeSH

Administration, Sublingual
Adult
Allergens
Animals
Bronchi
Child
Child, Preschool
Cytokines
Desensitization, Immunologic
Double-Blind Method
Dust
Epigenomics
Epithelial Cells
Female
Humans
Interleukin-1
Male
Mast Cells
Mites
Phleum
Rhinitis, Allergic, Seasonal
T-Lymphocytes, Regulatory
Th2 Cells
Treatment Outcome

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22677046