比较监测克罗恩病中英夫利昔单抗及抗英夫利昔单抗抗体的技术。

Comparison of techniques for monitoring infliximab and antibodies against infliximab in Crohn's disease.

机构信息

Department of Gastroenterology, Herlev Hospital, DK-2730 Herlev, Denmark.

出版信息

Ther Drug Monit. 2013 Aug;35(4):530-8. doi: 10.1097/FTD.0b013e31828d23c3.

DOI:10.1097/FTD.0b013e31828d23c3

PMID:23765033

Abstract

BACKGROUND

Several techniques are used to measure infliximab (IFX) and anti-IFX antibodies (Abs) in Crohn's disease. The aim of this study was to compare different assays for this purpose.

METHODS

Fluid-phase radioimmunoassay (RIA), solid-phase enzyme-linked immunosorbent assay (ELISA), reporter gene assay (RGA), and enzyme immunoassay (EIA; anti-IFX Ab only) were assessed. IFX was added to pooled serum from 13 patients with inactive Crohn's disease to yield concentrations of 0, 1, 3, and 9 µg/mL. Anti-IFX Abs were assessed in 6 patients.

RESULTS

IFX assessments: RIA and RGA had lower limit of detection than ELISA (0.07 µg/mL and 0.13 versus 0.26). Maximal inaccuracies were 39%, 24%, and 23%. Imprecisions (coefficients of variation) were ≤20% within IFX concentrations between 1 and 9 µg/mL. All assays showed linear correlations (R = 0.97-0.99), but sample concentrations differed by up to 1.55 µg/mL for RIA and RGA, 1.41 µg/mL for ELISA and RIA, and 0.48 µg/mL for ELISA and RGA (P < 0.05). Anti-IFX Ab assessments: RGA gave highly reproducible results (coefficients of variation ≤ 7%) compared with all others (24%-26%). All assays had linear correlations (R = 0.71-0.93), except ELISA versus RGA and EIA. Assays disagreed on anti-IFX Ab titers with mean difference -420 (-1200 to 210) in RGA and EIA, and up to 4500 (-2700 to 11,800) in RIA and RGA. A contributing factor to these discrepancies was inability of ELISA to detect IgG4 anti-IFX Abs.

CONCLUSIONS

Performances of assays for IFX and anti-IFX Abs are comparable. However, IFX concentrations and anti-IFX Ab titers show systematic differences, and in individual patients, only the same assay should be used. Problems may arise when different assays are used to manage therapies in the same patient.

摘要

背景

有几种技术可用于测量克罗恩病中的英夫利昔单抗（IFX）和抗 IFX 抗体（Abs）。本研究的目的是比较用于此目的的不同检测方法。

方法

评估液相反射免疫测定（RIA）、固相酶联免疫吸附测定（ELISA）、报告基因测定（RGA）和酶免疫测定（EIA；仅抗 IFX Ab）。将 IFX 添加到来自 13 名处于缓解期的克罗恩病患者的混合血清中，以产生 0、1、3 和 9 µg/mL 的浓度。在 6 名患者中评估抗 IFX Abs。

结果

IFX 评估：RIA 和 RGA 的检测下限低于 ELISA（0.07 µg/mL 和 0.13 与 0.26）。最大不准确性为 39%、24%和 23%。在 1 至 9 µg/mL 的 IFX 浓度范围内，精密度（变异系数）≤20%。所有检测均显示线性相关性（R = 0.97-0.99），但 RIA 和 RGA 的样品浓度差异最大可达 1.55 µg/mL，ELISA 和 RIA 的差异为 1.41 µg/mL，而 ELISA 和 RGA 的差异为 0.48 µg/mL（P < 0.05）。抗 IFX Ab 评估：与其他所有方法（24%-26%）相比，RGA 给出了高度可重复的结果（变异系数≤7%）。除 ELISA 与 RGA 和 EIA 外，所有检测均具有线性相关性（R = 0.71-0.93）。RGA 和 EIA 的抗 IFX Ab 滴度存在差异，平均差异为-420（-1200 至 210），而 RIA 和 RGA 的差异高达-4500（-2700 至 11800）。造成这些差异的一个因素是 ELISA 无法检测 IgG4 抗 IFX Abs。