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基于表面等离子体共振的抗阿达木单抗抗体鉴定及动力学表征方法。

Surface plasmon resonance-based methodology for anti-adalimumab antibody identification and kinetic characterization.

作者信息

Real-Fernández Feliciana, Cimaz Rolando, Rossi Giada, Simonini Gabriele, Giani Teresa, Pagnini Ilaria, Papini Anna Maria, Rovero Paolo

机构信息

Laboratory of Peptide and Protein Chemistry and Biology, Florence, Italy.

Department of Neurosciences, Psychology, Drug Research and Child Health - Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy.

出版信息

Anal Bioanal Chem. 2015 Sep;407(24):7477-85. doi: 10.1007/s00216-015-8915-8. Epub 2015 Jul 26.

Abstract

Adalimumab (ADA) is a TNF-α blocker drug antibody fully humanized and thus indistinguishable in structure and function from natural human IgG1, used in the juvenile idiopathic arthritis (JIA) treatment. Immunogenicity against the drug has been frequently detected in treated patients, and the presence of anti-ADA antibodies is correlated to treatment failure or lower clinical remission. Herein, we measured by surface plasmon resonance (SPR) both the binding and the affinity of anti-ADA antibodies to the ADA-immobilized biosensor. The binding of anti-ADA antibodies was evaluated by testing sera from ADA-treated patients (n = 30), untreated patients (n = 9), and healthy donors (n = 20) in the SPR biosensor. The optimal cut-off point was defined using the receiver operating characteristic curve (ROC-curve) analysis with 79 % (60.28 to 92.01 %, 95 % CI) sensitivity, 99 % (88.06 to 100.0 %, 95 % CI) specificity, and a positive likelihood ratio of 23. The area under the curve was 0.9298 (p < 0.0001). The apparent affinity of anti-ADA antibodies from pediatric patients' sera was measured, analyzing the interaction of anti-drug antibodies using whole sera, enriched IgG fractions, and isolated anti-ADA antibodies. The immobilized drug ADA interacted with purified antibodies at low affinities (10(-6) M > K D > 10(-9) M). Graphical Abstract Adalimumab immobilized on the biosensor chip surface detects specific anti-drug antibodies in treated patients' sera.

摘要

阿达木单抗(ADA)是一种肿瘤坏死因子-α阻断剂药物抗体,完全人源化,因此在结构和功能上与天然人IgG1无法区分,用于治疗青少年特发性关节炎(JIA)。在接受治疗的患者中经常检测到针对该药物的免疫原性,并且抗ADA抗体的存在与治疗失败或较低的临床缓解率相关。在此,我们通过表面等离子体共振(SPR)测量了抗ADA抗体与固定有ADA的生物传感器的结合及亲和力。通过在SPR生物传感器中检测ADA治疗患者(n = 30)、未治疗患者(n = 9)和健康供体(n = 20)的血清来评估抗ADA抗体的结合情况。使用受试者工作特征曲线(ROC曲线)分析定义最佳截断点,其灵敏度为79%(60.28%至92.01%,95%置信区间),特异性为99%(88.06%至100.0%,95%置信区间),阳性似然比为23。曲线下面积为0.9298(p < 0.0001)。通过分析使用全血清、富集的IgG组分和分离的抗ADA抗体的抗药物抗体相互作用,测量了儿科患者血清中抗ADA抗体的表观亲和力。固定化药物ADA与纯化抗体以低亲和力相互作用(10(-6) M > KD > 10(-9) M)。图形摘要:固定在生物传感器芯片表面的阿达木单抗检测治疗患者血清中的特异性抗药物抗体。

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