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花生 2S 白蛋白过敏原 Ara h 2 和 Ara h 6 是引发过敏反应的主要过敏原,可有效使花生过敏的小鼠脱敏。

The 2S albumin allergens of Arachis hypogaea, Ara h 2 and Ara h 6, are the major elicitors of anaphylaxis and can effectively desensitize peanut-allergic mice.

机构信息

Department of Pediatric Allergy and Immunology, Duke University Medical Center, Durham, NC, USA.

出版信息

Clin Exp Allergy. 2012 Feb;42(2):326-36. doi: 10.1111/j.1365-2222.2011.03934.x.

Abstract

BACKGROUND

Ara h 2 and Ara h 6, co-purified together in a 13-25 kD fraction (Ara h 2/6; 20 kD fraction) on gel filtration chromatography, account for the majority of effector activity in a crude peanut extract (CPE) when assayed with RBL SX-38 cells sensitized with IgE from human peanut allergic sera.

OBJECTIVES

To determine if Ara h 2/6 are the primary peanut allergens responsible for allergic reactions in vivo and to determine if Ara h 2/6 would be sufficient to prevent allergic reactions to a complete CPE.

METHODS

An oral sensitization mouse model of peanut allergy was used to assess the activity of Ara h 2/6 (20 kD) and CPE without the 20 kD fraction (CPE w/o 20 kD) for allergic provocation challenge and immunotherapy. The activity of these preparations was also tested in an assay of histamine release from human basophils in whole blood.

RESULTS

Compared with mice challenged with control CPE, mice challenged with CPE w/o 20 kD experienced reduced symptoms (P < 0.05) and a smaller decrease in body temperature (P < 0.01). Results with the basophil histamine release assay corroborated these findings (P < 0.01). The mouse model was also used to administer Ara h 2/6 (20 kD) in an immunotherapy protocol, in which peanut-allergic mice treated with the 20 kD fraction experienced significantly reduced symptoms, changes in body temperature, and mast cell protease (MMCP-1) release compared with placebo (P < 0.01 for all parameters). Importantly, immunotherapy with the 20 kD fraction was just as effective as treatment with CPE, whereas CPE w/o 20 kD was significantly less effective for higher dose peanut challenges.

CONCLUSIONS AND CLINICAL RELEVANCE

Ara h 2/6 are the most potent peanut allergens in vivo and can be used to desensitize peanut-allergic mice. These results have potential implications for clinical research in the areas of diagnosis and immunotherapy for peanut allergy.

摘要

背景

Ara h 2 和 Ara h 6 在凝胶过滤层析中共同纯化在 13-25 kD 级分(Ara h 2/6;20 kD 级分)中,当用 IgE 从人类花生过敏血清致敏的 RBL SX-38 细胞测定时,占粗花生提取物(CPE)中的大多数效应物活性。

目的

确定 Ara h 2/6 是否是导致体内过敏反应的主要花生过敏原,并确定 Ara h 2/6 是否足以预防对完整 CPE 的过敏反应。

方法

使用口服致敏的花生过敏小鼠模型来评估 Ara h 2/6(20 kD)和无 20 kD 级分的 CPE(CPE w/o 20 kD)在过敏激发挑战和免疫治疗中的活性。还在全血中从人嗜碱性粒细胞释放组胺的测定中测试了这些制剂的活性。

结果

与用对照 CPE 挑战的小鼠相比,用 CPE w/o 20 kD 挑战的小鼠经历的症状减轻(P <0.05),体温下降幅度较小(P <0.01)。嗜碱性粒细胞组胺释放测定的结果证实了这些发现(P <0.01)。该小鼠模型还用于在免疫治疗方案中给予 Ara h 2/6(20 kD),用 20 kD 级分治疗的花生过敏小鼠与安慰剂相比,症状明显减轻,体温变化和肥大细胞蛋白酶(MMCP-1)释放减少(所有参数 P <0.01)。重要的是,20 kD 级分的免疫治疗与 CPE 一样有效,而没有 20 kD 级分的 CPE 对较高剂量的花生挑战则效果明显较差。

结论和临床相关性

Ara h 2/6 是体内最有效的花生过敏原,可用于使花生过敏的小鼠脱敏。这些结果对于花生过敏的诊断和免疫治疗领域的临床研究具有潜在意义。

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