Heinrich-Heine-Universität, Moorenstraße 5, Düsseldorf 40225, Germany.
J Neuroinflammation. 2012 Jun 15;9:129. doi: 10.1186/1742-2094-9-129.
Interferon-beta (IFNB) therapy for multiple sclerosis can lead to the induction of neutralizing antibodies (NAbs) against IFNB. Various methods are used for detection and quantification of NAbs.
Blood samples from 125 IFNB-1b-treated patients, which were tested NAb negative or NAb positive after conclusion of a clinical study, were retested three years after first being assessed in four different laboratories that offer routine NAb testing to practicing neurologists. The myxovirus protein A (MxA) induction assay, the cytopathic effect (CPE) assay (two laboratories), or the luciferase assay were used. Intra- and inter-laboratory agreement between assays with respect to NAb detection and NAb titer quantification were evaluated.
High agreement for NAb detection (kappa coefficient, 0.86) and for titer levels was observed for the intra-laboratory comparison in the laboratory using the MxA induction assay performed three years ago and now. A similarly high agreement for NAb detection (kappa coefficient, 0.87) and for titer quantification was noted for the MxA assay of this laboratory with one of two laboratories using the CPE assay. All other inter-laboratory comparisons showed kappa values between 0.57 and 0.68 and remarkable differences in individual titer levels.
There are considerable differences in the detection and quantification of IFNB-induced NAbs among laboratories offering NAb testing for clinical practice using different assay methods. It is important that these differences are considered when interpreting NAb results for clinical decision-making and when developing general recommendations for potentially clinically meaningful NAb titer levels.
干扰素-β（IFNB）治疗多发性硬化症可导致针对 IFNB 的中和抗体（NAb）的诱导。有多种方法用于检测和定量 NAb。
对 125 名接受 IFNB-1b 治疗的患者的血样进行了检测，这些患者在一项临床研究结束后被检测为 NAb 阴性或 NAb 阳性，然后在 3 年后，在四个提供常规 NAb 检测给执业神经科医生的不同实验室中进行了重新检测。使用肌病毒蛋白 A（MxA）诱导测定法、细胞病变效应（CPE）测定法（两个实验室）或荧光素酶测定法进行检测。评估了各实验室之间在检测 NAb 和定量 NAb 滴度方面的内部和实验室间的一致性。
在使用 MxA 诱导测定法进行的内部比较中，观察到 NAb 检测（kappa 系数，0.86）和滴度水平的高度一致性，该实验室三年前进行了检测，现在又进行了检测。在该实验室使用 CPE 测定法的两个实验室之一进行的 MxA 测定中，也观察到 NAb 检测（kappa 系数，0.87）和滴度定量的高度一致性。所有其他实验室间比较显示 kappa 值在 0.57 到 0.68 之间，并且在个别滴度水平上存在显著差异。
在使用不同测定方法为临床实践提供 NAb 检测的实验室中，IFNB 诱导的 NAb 的检测和定量存在相当大的差异。在进行临床决策时解释 NAb 结果以及制定潜在具有临床意义的 NAb 滴度水平的一般建议时，必须考虑到这些差异。
