Department of Immunopathology, Sanquin Research and Landsteiner Laboratory Academic Medical Centre, Amsterdam, The Netherlands.
J Immunol Methods. 2010 Oct 31;362(1-2):82-8. doi: 10.1016/j.jim.2010.09.005. Epub 2010 Sep 9.
Production of anti drug antibodies (ADA) in adalimumab treated RA patients is associated with reduced serum adalimumab levels and less clinical response. However, most current assays to measure ADA are unable to detect ADA in complex with adalimumab. Thus, ADA is only measured if antibody production exceeds drug levels in the serum, meaning that ADA formation is underestimated. The aim of this study is to develop a method to detect ADA in the presence of drug. A pH-shift-anti-idiotype Antigen binding test (PIA) was used to enable ADA measurement in the presence of adalimumab. ADA-adalimumab complexes were dissociated by acid treatment and addition of excess rabbit anti-idiotype-F(ab) before neutralization. Rabbit anti-idiotype-F(ab) blocks reformation of ADA-drug complexes by competing with patient ADA for adalimumab binding. Released ADA are measured by an antigen binding test (ABT). The PIA enabled detection of ADA in the presence of large excess of adalimumab and was used to measure ADA in 30 adalimumab treated rheumatoid arthritis (RA) patients during the first 28 weeks of treatment. It revealed ADA in 21 out of 30 tested patients, while the ABT detected ADA in only 5 patients. Indicating that an immunogenic reaction towards adalimumab is present in the majority of adalimumab treated patients.
在接受阿达木单抗治疗的类风湿关节炎（RA）患者中，产生抗药物抗体（ADA）与血清阿达木单抗水平降低和临床反应减少有关。然而，目前大多数用于测量 ADA 的检测方法都无法检测到与阿达木单抗结合的 ADA。因此，只有当抗体产生超过血清中的药物水平时才会测量 ADA，这意味着 ADA 的形成被低估了。本研究的目的是开发一种在有药物存在的情况下检测 ADA 的方法。采用 pH 转换-抗独特型抗原结合试验（PIA）来实现 ADA 在阿达木单抗存在的情况下的测量。通过酸处理和添加过量兔抗独特型 F(ab)来解离 ADA-阿达木单抗复合物，然后再中和。兔抗独特型 F(ab)通过与患者 ADA 竞争阿达木单抗结合来阻止 ADA-药物复合物的重新形成。通过抗原结合试验（ABT）测量释放的 ADA。PIA 能够在大量阿达木单抗存在的情况下检测 ADA，并用于在治疗的前 28 周内检测 30 名接受阿达木单抗治疗的类风湿关节炎患者中的 ADA。结果显示，在 30 名检测患者中有 21 名产生了 ADA，而 ABT 仅检测到 5 名患者产生了 ADA。这表明在大多数接受阿达木单抗治疗的患者中存在针对阿达木单抗的免疫反应。
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