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.
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.
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DOI：
10.1111/cea.12936
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发表时间：
2017-08
期刊：
影响因子：
--
通讯作者：
Li XM
中科院分区：
文献类型：
--
作者：
Srivastava KD;Song Y;Yang N;Liu C;Goldberg IE;Nowak-Węgrzyn A;Sampson HA;Li XM
同时对花生（PN）和树坚果（TN）敏感，最危险的食物过敏，是常见的。目前口服免疫治疗（OIT）并不完全令人满意。确定草药配方B-FAHF-2 （BF2）是否能改善PN/TN OIT不良反应并增强耐受性状态的持久性。同时致敏的花生、核桃（WN）和腰果（CSH）过敏小鼠接受1天PN/WN/CSH快速OIT加3周维持剂量，前3周和3周BF2联合治疗或不联合治疗。测定过敏症状评分、核心体温、血浆组胺水平、嗜碱性粒细胞数量、抗原特异性IgE、细胞因子水平、IL-4、INF-γ和Foxp3基因启动子DNA甲基化状态及其与最终激药症状评分的相关性。BF2+OIT处理小鼠在1天的快速OIT积累剂量期出现的不良反应明显少于单纯OIT处理小鼠（p<0.01）。在治疗后1周，仅OIT和BF2+OIT小鼠均表现出显著的脱敏（p分别<0.01和0.001）；在BF2+OIT小鼠中更大。所有假药治疗和91%的OIT治疗小鼠出现过敏反应，而BF2+OIT治疗小鼠只有21%在5-6周的剂量递增单次PN和TN刺激期间出现反应。在BF2+OIT小鼠中，更强和更持久的保护与血浆组胺和IgE水平显著降低、IFN-γ /IL-4和IL-10/IL-4比率升高、IL-4启动子DNA重甲基化和IFN-γ和Foxp3启动子DNA去甲基化相关。最终激战症状评分与IL-4 DNA甲基化水平呈负相关（p<0.0002），与IFN-γ和Foxp3基因启动子甲基化水平呈正相关（p<0.0011） （p<0.0165）。与单独使用OIT相比，BF2/OIT联合治疗更安全，产生更长的治疗后保护，更容易产生耐受性的免疫和表观遗传修饰。BF2/OIT可能为同时对花生/树坚果和其他食物过敏的患者提供额外的OIT选择。
Concurrent sensitization to peanut (PN) and tree nuts (TN), the most dangerous food allergies, is common. Current oral immunotherapy (OIT) is not fully satisfactory. To determine if the herbal formula B-FAHF-2 (BF2) ameliorates PN/TN OIT adverse reactions and enhances persistence of a tolerant state. 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. 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). 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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DOI：
10.1016/j.jaci.2010.10.007
发表时间：
2010-12
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
NIAID-Sponsored Expert Panel;Boyce JA;Assa'ad A;Burks AW;Jones SM;Sampson HA;Wood RA;Plaut M;Cooper SF;Fenton MJ;Arshad SH;Bahna SL;Beck LA;Byrd-Bredbenner C;Camargo CA Jr;Eichenfield L;Furuta GT;Hanifin JM;Jones C;Kraft M;Levy BD;Lieberman P;Luccioli S;McCall KM;Schneider LC;Simon RA;Simons FE;Teach SJ;Yawn BP;Schwaninger JM
通讯作者：
Schwaninger JM
影响因子：
2.8
作者：
Beigelman, Avraham;Strunk, Robert C.;Bacharier, Leonard B.
通讯作者：
Bacharier, Leonard B.
影响因子：
5.6
作者：
Liu C;Yang N;Song Y;Wang L;Zi J;Zhang S;Dunkin D;Busse P;Weir D;Tversky J;Miller RL;Goldfarb J;Zhan J;Li XM
通讯作者：
Li XM
影响因子：
14.2
作者：
Gorelik, Mark;Narisety, Satya D.;Frischmeyer-Guerrerio, Pamela A.
通讯作者：
Frischmeyer-Guerrerio, Pamela A.
影响因子：
14.2
作者：
Leonard, Stephanie A.;Martos, Gustavo;Wang, Wei;Nowak-Wegrzyn, Anna;Berin, M. Cecilia
通讯作者：
Berin, M. Cecilia