Abstract

BackgroundImproving the safety of subcutaneous immunotherapy (SCIT) for food allergy is necessary to reduce side effects and achieve long-term tolerance. We determined the effect of dietary supplementation with 1% non-digestible short- and long-chain fructo-oligosaccharides (scFOS/lcFOS) on safety and efficacy of SCIT using a peanut allergy mouse model.MethodsAfter sensitization, mice received a scFOS/lcFOS or control diet for the rest of the study. To study safety of SCIT, mice were dosed with a single subcutaneous injection of peanut extract (PE) or PBS. To study efficacy, mice were dosed subcutaneously (SCIT, 3 times/week) with PE or PBS for 3 weeks. Hereafter, acute allergic skin responses, anaphylactic shock symptoms and body temperature were assessed. To study the mechanism in vitro, the human IgE receptor (FcεRI)-transfected rat mast cell (RBL) line was sensitized with an oligoclonal pool of chimeric human (chu)IgE antibodies against bovine β-lactoglobulin (BLG) and incubated with the oligosaccharides before exposure to BLG to assess direct the effect on degranulation.ResultsscFOS/lcFOS reduced anaphylaxis caused by a single PE SCIT dose. scFOS/lcFOS alone also reduced the acute allergic skin response. Moreover, scFOS/lcFOS supplementation resulted in lower MMCP-1 levels in serum after PE SCIT dose compared to control diet, while antibody levels were not affected by the diet. In vitro incubation with scFOS/lcFOS at 0.5% suppressed the degranulation of IgE-sensitized RBL cells. However, dietary supplementation with scFOS/lcFOS did not improve the efficacy of SCIT.ConclusionsWe show that scFOS/lcFOS diet improves the safety of SCIT, as evidenced by lower anaphylactic responses without compromising the efficacy in a mouse model for peanut allergy. This effect is likely to result from the suppression of mast cell effector function.

Highlights

  • Improving the safety of subcutaneous immunotherapy (SCIT) for food allergy is necessary to reduce side effects and achieve long-term tolerance

  • Results short-chain fructo-oligosaccharides (scFOS)/long-chain fructo-oligosaccharides (lcFOS) reduced anaphylaxis and mast cell degranulation after SCIT peanut extract (PE) dose The protective effect of scFOS/lcFOS supplementation to reduce side effects induced by SCIT was examined by analyzing allergic responses after one SCIT PE dose (Fig. 2)

  • A single dose of 100 μg s.c. caused an anaphylactic response in PE-sensitized mice, measured by a severe drop in body temperature and high anaphylactic symptom scores compared to the mice receiving a PBS dose (Fig. 2a, b)

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Summary

Introduction

Improving the safety of subcutaneous immunotherapy (SCIT) for food allergy is necessary to reduce side effects and achieve long-term tolerance. We determined the effect of dietary supplementation with 1% nondigestible short- and long-chain fructo-oligosaccharides (scFOS/lcFOS) on safety and efficacy of SCIT using a peanut allergy mouse model. AIT using the subcutaneous, oral, or sublingual route provided encouraging results in food allergy, despite serious and significant safety concerns [2,3,4,5,6,7,8]. A high rate of serious systemic reactions (13%) made this treatment unsafe for routine use. Because of these limitations, effective, it is currently not recommended to use immunotherapy for peanut allergy for routine clinical use [11,12,13]

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