TY - JOUR
T1 - 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
AU - Srivastava, K. D.
AU - Song, Y.
AU - Yang, N.
AU - Liu, C.
AU - Goldberg, I. E.
AU - Nowak-Węgrzyn, A.
AU - Sampson, H. A.
AU - Li, X. M.
N1 - Funding Information:
Funding source: This study was supported by NIH/NCCIH grant #1R01AT001495-01A1 and 2R01 AT001495-05A1, the Food Allergy Initiative, the Winston Wolkoff Fund for Integrative Medicine for Allergies and Wellness as well as the contributions from Susan and Andrew Weissman, Selena Blunzer and family, Deirdre Olsen, Barbara and Tom O'Shea, Jill and Eric Li, Anna Sherbakova and family, Edina and David Yee and Mille Wong and family to Dr. Xiu-Min Li's research. KD Srivastava received salary support through KL2 Faculty Scholar Award KL2TR000069 from Mount Sinai Clinical and Translational Award (CTSA). Authors thank Brian Schofield for discussion and revision of the manuscript. The authors also wish to thank all families who have been supportive of the project “Chinese herbal medicine for food allergy.”
Publisher Copyright:
© 2017 John Wiley & Sons Ltd
PY - 2017/8
Y1 - 2017/8
N2 - 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 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 PN/TN and other food allergies.
AB - 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 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 PN/TN and other food allergies.
KW - B-FAHF-2
KW - Chinese herbal medicine
KW - Food allergies
KW - cytokines and epigenetic regulation
KW - murine model of peanut allergies and tree nut allergies
KW - oral immunotherapy
UR - http://www.scopus.com/inward/record.url?scp=85019176501&partnerID=8YFLogxK
U2 - 10.1111/cea.12936
DO - 10.1111/cea.12936
M3 - Article
C2 - 28397379
AN - SCOPUS:85019176501
SN - 0954-7894
VL - 47
SP - 1038
EP - 1049
JO - Clinical and Experimental Allergy
JF - Clinical and Experimental Allergy
IS - 8
ER -