title: 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 whether the herbal formula B-FAHF-2 (BF2) 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 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<.01) during the 1-day rush OIT build-up dose phase. Both OIT-only and BF2+OIT mice showed significant desensitization (P<.01 and .001, respectively) at 1 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 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
  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 PN/TN and other food allergies.
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Srivastava
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: N
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: C
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: I E
authors.initials: IE
authors.lastname: Goldberg
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: A
authors.initials: A
authors.lastname: Nowak-Węgrzyn
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Sampson
authors.affiliation: Department of Pediatrics, Jaffe Food Allergy Institute, Center for Integrative Medicine for Immunology and Wellness, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: X-M
authors.identifier: http://orcid.org/0000-0002-6207-2427
authors.initials: XM
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000276:immunology; D007073:Immunoglobulin E / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D021184:Nut Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000628:therapy; D021183:Peanut Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000628:therapy; D028321:Plant Preparations / Q000494:pharmacology*
chemical_list: D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; C000611649:IFNG protein, mouse; D028321:Plant Preparations; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma
keywords: B-FAHF-2; Chinese herbal medicine; Food allergies; cytokines and epigenetic regulation; murine model of peanut allergies and tree nut allergies; oral immunotherapy