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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
Author(s) -
Srivastava K. D.,
Song Y.,
Yang N.,
Liu C.,
Goldberg I. E.,
NowakWęgrzyn A.,
Sampson H. A.,
Li X.M.
Publication year - 2017
Publication title -
clinical and experimental allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 154
eISSN - 1365-2222
pISSN - 0954-7894
DOI - 10.1111/cea.12936
Subject(s) - medicine , allergy , immunoglobulin e , anaphylaxis , sensitization , desensitization (medicine) , immunology , oral immunotherapy , adverse effect , basophil , gastroenterology , food allergy , antibody , receptor
Summary 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 whether the herbal formula B‐ FAHF ‐2 ( BF 2) ameliorates PN / TN OIT adverse reactions and enhances persistence of a tolerant state. Methods Concurrently sensitized PN‐, 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 BF 2 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 BF 2+ OIT ‐treated mice experienced significantly fewer and less severe adverse reactions than OIT ‐only‐treated mice ( P <.01) during the 1‐day rush OIT build‐up dose phase. Both OIT ‐only and BF 2+ OIT mice showed significant desensitization ( P <.01 and .001, respectively) at 1 week post‐therapy challenge, being greater in BF 2+ OIT mice. All sham‐treated and 91% of OIT ‐treated mice experienced anaphylaxis whereas only 21% of BF 2+ OIT ‐treated mice exhibited reactions during 5‐6 weeks of dose escalation single PN and TN challenges. Greater and more persistent protection in BF 2+ OIT mice was associated with significantly lower plasma histamine and IgE levels, increased IFN ‐γ/ IL ‐4 and IL ‐10/ IL ‐4 ratios, DNA remethylation at the IL ‐4 promoter and demethylation at IFN ‐γ and Foxp3 promoters. Final challenge symptom scores were inversely correlated with IL ‐4 DNA methylation levels ( P <.0002) and positively correlated with IFN ‐γ and Foxp3 gene promoter methylation levels ( P <.0011) ( P <.0165). Conclusions and Clinical Relevance Combined BF 2/ OIT therapy was safer and produced longer post‐treatment protection and more tolerance‐prone immunological and epigenetic modifications than OIT alone. BF 2/ OIT may provide an additional OIT option for patients with concurrent PN/TN and other food allergies.