B-FAHF-2 plus oral immunotherapy (OIT) is safer and more effective than OIT alone in a murine model of concurrent peanut/tree nut allergy

Abstract

Background

Concurrent sensitization to peanut (PN) and tree nuts (TN), the most dangerous food allergies, is common. Current oral immunotherapy (OIT) is not fully satisfactory.

Objective

To determine if the herbal formula B-FAHF-2 (BF2) ameliorates PN/TN OIT adverse reactions and enhances persistence of a tolerant state.

Methods

Concurrently sensitized peanut, walnut (WN) and cashew (CSH) allergic mice received 1 day PN/WN/CSH rush OIT plus 3 weeks of maintenance dosing, with or without 3-weeks prior and 3-weeks BF2 co-treatment. Anaphylactic symptom scores, core body temperatures, plasma histamine levels, basophil numbers, antigen-specific IgE, cytokine levels, and IL-4, INF-γ and Foxp3 gene promoter DNA methylation status, and their correlation with final challenge symptom scores were determined.

Results

BF2+OIT treated mice experienced significantly fewer and less severe adverse reactions than OIT only treated mice (p<0.01) during the one-day rush OIT buildup dose phase. Both OIT only and BF2+OIT mice showed significant desensitization (p<0.01 and 0.001 respectively) at one-week post therapy challenge; being greater in BF2+OIT mice. All sham treated and 91% of OIT treated mice experienced anaphylaxis whereas only 21% of BF2+OIT treated mice exhibited reactions during 5-6 weeks of dose escalation single PN and TN challenges. Greater and more persistent protection in BF2+OIT mice was associated with significantly lower plasma histamine and IgE levels, increased IFN- γ/IL-4 and IL-10/IL-4 ratios, DNA re-methylation at the IL-4 promoter and de-methylation at IFN-γ and Foxp3 promoters. Final challenge symptom scores were inversely correlated with IL-4 DNA methylation levels (p<0.0002), and positively correlated with IFN-γ and Foxp3 gene promoter methylation levels (p<0.0011) (p<0.0165).

Conclusions and clinical relevance

Combined BF2/OIT therapy was safer and produced longer post treatment protection, and more tolerance-prone immunological and epigenetic modifications than OIT alone. BF2/OIT may provide an additional OIT option for patients with concurrent peanut/ tree nut and other food allergies.

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