Abstract:

The detection of small molecule haptens is of great significance for food and drug testing， environmental monitoring and disease diagnosis. However， commercially available immunoassays for haptens are limited， partially due to poor performance， such as low sensitivity. In the early 20th century， anti-idiotypes （Ab2） were discovered， and Ab2 can be divided into three different isoforms： Ab2α， Ab2β and Ab2γ. In addition to be used for the treatment and prevention of disease， Ab2 has potential applications in immunoassays. This review provided an overview of the use of Ab2 in competitive， non-competitive and phage-based immunoassays， including the different detection formats and effects on the performance. Both the use of appropriate Ab2 instead of hapten derivatives in competitive assays and the use of anti-metatype antibodies against primary antibody and hapten complexes in non-competitive assays could increase detection sensitivity and improve cross-reactivity. The use of Ab2 could be a potentially important choice for the development of in vitro diagnostic assays in the future. In addition， different methods for the generation of Ab2 were summarized. The selection of natural nanobody libraries might be a more practical way to obtain Ab2 than traditional monoclonal antibody production.

Key words: anti-idiotypes, hapten, immunoassay, nanobody library

摘要：

小分子半抗原的检测在食品药品检验、环境检测和疾病诊断等领域具有重要意义，但目前针对半抗原的免疫检测在灵敏度方面表现欠佳。抗独特型抗体（anti-idiotypes，Ab2）发现于20世纪初，主要分为3种亚型：Ab2α、Ab2β和Ab2γ。Ab2除了可以用于预防和治疗疾病外，在免疫检测中也有潜在的应用价值。概述了Ab2在竞争性、非竞争性及基于噬菌体免疫分析中的应用，包括检测模式及效果。无论是在竞争法中采用合适的Ab2替代半抗原衍生物，还是在非竞争法中采用针对一抗和半抗原复合物的抗伴型抗体，都能提高检测灵敏度，改善交叉率。Ab2的应用是未来体外诊断试剂盒开发的一个重要思路。此外，还对目前Ab2的几种开发方法进行了分析，较之传统抗体开发技术，天然纳米抗体库可能是获取Ab2更为实用的一种方式。

关键词: 抗独特型抗体, 半抗原, 免疫分析, 纳米抗体库