Franke Bernd, Galloway Tamara S, Wilkin Terry J
Department of Diabetes/Endocrinology Level D, Rotherham General Hospital, UK.
Diabetes Metab Res Rev. 2005 Sep-Oct;21(5):395-415. doi: 10.1002/dmrr.554.
The prodromal phase of type 1 diabetes is characterised by the appearance of multiple islet-cell related autoantibodies (Aab). The major target antigens are islet-cell antigen, glutamic acid decarboxylase (GAD), protein-tyrosine phosphatase-2 (IA-2) and insulin. Insulin autoantibodies (IAA), in contrast to the other autoimmune markers, are the only beta-cell specific antibodies. There is general consensus that the presence of multiple Aab (> or = 3) is associated with a high risk of developing diabetes, where the presence of a single islet-cell-related Aab has usually a low predictive value. The most commonly used assay format for the detection of Aab to GAD, IA-2 and insulin is the fluid-phase radiobinding assay. The RBA does not identify or measure Aab, but merely detects its presence. However, on the basis of molecular studies, disease-specific constructs of GAD and IA-2 have been employed leading to somewhat improved sensitivity and specificity of the RBA. Serological studies have shown epitope restriction of IAA that can differentiate diabetes-related from unrelated IAA, but current assays do not distinguish between disease-predictive and non-predictive IAA or between IAA and insulin antibodies (IA). More recently, phage display technology has been successful in identifying disease-specific anti-idiotopes of insulin. In addition, phage display has facilitated the in vitro production of antibodies with high affinity. Identification of disease-specific anti-idiotopes of insulin should enable the production of a high affinity reagent against the same anti-idiotope. Such a development would form the basis of a disease-specific radioimmunoassay able to identify and measure particular idiotypes, rather than merely detect and titrate IAA.
1型糖尿病的前驱期特征是出现多种胰岛细胞相关自身抗体（Aab）。主要靶抗原是胰岛细胞抗原、谷氨酸脱羧酶（GAD）、蛋白酪氨酸磷酸酶-2（IA-2）和胰岛素。与其他自身免疫标志物不同，胰岛素自身抗体（IAA）是唯一的β细胞特异性抗体。人们普遍认为，多种Aab（≥3种）的存在与患糖尿病的高风险相关，而单一胰岛细胞相关Aab的存在通常预测价值较低。检测针对GAD、IA-2和胰岛素的Aab最常用的检测方法是液相放射结合分析。放射结合分析不能识别或测量Aab，而仅仅检测其存在。然而，基于分子研究，已采用GAD和IA-2的疾病特异性构建体，从而在一定程度上提高了放射结合分析的敏感性和特异性。血清学研究表明IAA存在表位限制，这可以区分糖尿病相关和非相关的IAA，但目前的检测方法无法区分疾病预测性和非预测性IAA，也无法区分IAA和胰岛素抗体（IA）。最近，噬菌体展示技术已成功鉴定出胰岛素的疾病特异性抗独特型。此外，噬菌体展示促进了高亲和力抗体的体外生产。鉴定胰岛素的疾病特异性抗独特型应能产生针对同一抗独特型的高亲和力试剂。这样的进展将构成一种疾病特异性放射免疫分析的基础，该分析能够识别和测量特定的独特型，而不仅仅是检测和滴定IAA。
