Department of Immunopathology, Sanquin Research and Landsteiner Laboratory AMC, Amsterdam, The Netherlands.
J Immunol Methods. 2011 Sep 30;372(1-2):196-203. doi: 10.1016/j.jim.2011.07.019. Epub 2011 Jul 29.
The presence of anti-drug antibodies (ADA) in adalimumab-treated patients is associated with reduced serum adalimumab levels and a lower clinical response. Currently, there is no standard for measurement of anti-drug antibodies and many factors influence the results. Consequently, the incidence of ADA as reported in different studies varies considerably. Here we investigated the differential effect of drug interference in two common types of assays used to measure anti-adalimumab: an antigen binding test (ABT) and a more often-used bridging elisa. We measured ADA to adalimumab in a cohort of 216 rheumatoid arthritis patients treated with adalimumab for 28 weeks. Only 15 samples (7%) were positive in the bridging elisa, compared to 29 (13%) in the ABT, despite the fact that the bridging elisa was the most sensitive assay. Furthermore, in an ABT specific for IgG4, 48 samples (22%) were found positive. The bridging elisa was found to detect only the bivalent form of (drug-specific) IgG4, resulting in an underestimation of ADA levels. However, the predominant reason for the different outcomes of these assays was a differential susceptibility to drug interference. In particular, the bridging elisa only detected ADA in the absence of detectable amounts of circulating adalimumab and is therefore not suited for measurement of ADA in complex with the drug. In summary, we showed that a bridging elisa is susceptible to drug interference and typically measures ADA only in absence of detectable drug levels.
抗药物抗体（ADA）在阿达木单抗治疗患者中的存在与血清阿达木单抗水平降低和临床反应降低有关。目前，尚没有测量抗药物抗体的标准，并且许多因素会影响结果。因此，不同研究报告的 ADA 发生率差异很大。在这里，我们研究了两种常用的测定抗阿达木单抗的方法中药物干扰的差异效应：抗原结合试验（ABT）和更常用的桥接 ELISA。我们在接受阿达木单抗治疗 28 周的 216 例类风湿关节炎患者中测定了 ADA。尽管桥接 ELISA 是最敏感的检测方法，但仅在 15 份（7％）样品中发现 ADA 阳性，而在 ABT 中则有 29 份（13％）阳性。此外，在针对 IgG4 的 ABT 中，有 48 份（22％）被发现阳性。桥接 ELISA 仅检测到（药物特异性）IgG4 的二价形式，从而导致 ADA 水平的低估。但是，这些检测结果不同的主要原因是对药物干扰的敏感性不同。特别是，桥接 ELISA 仅在检测不到循环阿达木单抗的情况下才检测 ADA，因此不适合测量与药物结合的 ADA。综上所述，我们表明桥接 ELISA 易受药物干扰，并且通常仅在检测不到药物水平的情况下测量 ADA。
