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结构生物学、诊断与免疫治疗中的重组变应原

Recombinant Allergens in Structural Biology, Diagnosis, and Immunotherapy.

作者信息

Tscheppe Angelika, Breiteneder Heimo

机构信息

Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria.

出版信息

Int Arch Allergy Immunol. 2017;172(4):187-202. doi: 10.1159/000464104. Epub 2017 May 4.

Abstract

The years 1988-1995 witnessed the beginning of allergen cloning and the generation of recombinant allergens, which opened up new avenues for the diagnosis and research of human allergic diseases. Most crystal and solution structures of allergens have been obtained using recombinant allergens. Structural information on allergens allows insights into their evolutionary biology, illustrates clinically observed cross-reactivities, and makes the design of hypoallergenic derivatives for allergy vaccines possible. Recombinant allergens are widely used in molecule-based allergy diagnosis such as protein microarrays or suspension arrays. Recombinant technologies have been used to produce well-characterized, noncontaminated vaccine components with known biological activities including a variety of allergen derivatives with reduced IgE reactivity. Such recombinant hypoallergens as well as wild-type recombinant allergens have been used successfully in several immunotherapy trials for more than a decade to treat birch and grass pollen allergy. As a more recent application, the development of antibody repertoires directed against conformational epitopes during immunotherapy has been monitored by recombinant allergen chimeras. Although much progress has been made, the number and quality of recombinant allergens will undoubtedly increase and keep improving our knowledge in basic scientific investigations, diagnosis, and therapy of human allergic diseases.

摘要

1988年至1995年间见证了变应原克隆的开端以及重组变应原的产生,这为人类过敏性疾病的诊断和研究开辟了新途径。大多数变应原的晶体结构和溶液结构都是使用重组变应原获得的。变应原的结构信息有助于深入了解其进化生物学,阐明临床观察到的交叉反应性,并使设计用于过敏疫苗的低变应原性衍生物成为可能。重组变应原广泛应用于基于分子的过敏诊断,如蛋白质微阵列或悬浮阵列。重组技术已用于生产具有明确特征、无污染且具有已知生物活性的疫苗成分,包括多种IgE反应性降低的变应原衍生物。此类重组低变应原以及野生型重组变应原已在多项免疫治疗试验中成功应用了十多年,用于治疗桦树和草花粉过敏。作为一项最新应用,重组变应原嵌合体已用于监测免疫治疗期间针对构象表位的抗体库的发展。尽管已取得很大进展,但重组变应原的数量和质量无疑将增加,并不断增进我们对人类过敏性疾病基础科学研究、诊断和治疗的认识。

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