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)
Summary
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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