Coagulation Laboratory, Ghent University Hospital, Ghent, Belgium.
Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
J Thromb Haemost. 2022 Feb;20(2):508-524. doi: 10.1111/jth.15585. Epub 2021 Dec 2.
Antiβ2glycoprotein I (aβ2GPI) and anticardiolipin (aCL) IgG/IgM show differences in positive/negative agreement and titers between solid phase platforms. Method-specific semiquantitative categorization of titers could improve and harmonize the interpretation across platforms.
To evaluate the traditional 40/80-unit thresholds used for aCL and aβ2GPI for categorization into moderate/high positivity with different analytical systems, and to compare with alternative thresholds.
aCL and aβ2GPI thresholds were calculated for two automated systems (chemiluminescent immunoassay [CLIA] and multiplex flow immunoassay [MFI]) by receiver operating characteristic curve analysis on 1108 patient samples, including patients with and without antiphospholipid syndrome (APS), and confirmed on a second population (n = 279). Alternatively, regression analysis on diluted standard material was applied to identify thresholds. Thresholds were compared to 40/80 threshold measured by an enzyme-linked immunosorbent assay (ELISA). Additionally, likelihood ratios (LR) were calculated.
Threshold levels of 40/80 units show poor agreement between ELISA and automated platforms for classification into low/moderate/high positivity, especially for aCL/aβ2GPI IgG. Agreement for semiquantitative interpretation of antiphospholipid antibodies (aPL) IgG between ELISA and CLIA/MFI improves with alternative thresholds. LR for aPL IgG increase for thrombotic and obstetric APS based on 40/80 thresholds for ELISA and adapted thresholds for the other systems, but not for IgM.
Use of 40/80 units as medium/high thresholds is acceptable for aCL/aβ2GPI IgG ELISA, but not for CLIA and MFI. Alternative semiquantitative thresholds for non-ELISA platforms can be determined by a clinical approach or by using monoclonal antibodies. Semiquantitative reporting of aPL IgM has less impact on increasing probability for APS.
抗β2 糖蛋白 I（aβ2GPI）和抗心磷脂（aCL）IgG/IgM 在固相平台之间的阳性/阴性一致性和滴度存在差异。针对特定方法的半定量分类可以提高和协调平台之间的解释。
评估用于 aCL 和 aβ2GPI 的传统 40/80 单位阈值，以将不同分析系统的中度/高度阳性进行分类，并与替代阈值进行比较。
通过对 1108 例患者样本（包括有和无抗磷脂综合征 [APS] 的患者）的接受者操作特征曲线分析，计算了两种自动化系统（化学发光免疫分析 [CLIA] 和多重流式免疫分析 [MFI]）的 aCL 和 aβ2GPI 阈值，并在第二个患者群体（n=279）中进行了验证。或者，应用稀释标准物质的回归分析来确定阈值。将阈值与酶联免疫吸附测定（ELISA）测量的 40/80 阈值进行比较。此外，还计算了可能性比（LR）。
对于分类为低/中/高阳性，ELISA 和自动化平台之间的 40/80 单位阈值显示出较差的一致性，特别是对于 aCL/aβ2GPI IgG。ELISA 和 CLIA/MFI 之间半定量解释抗磷脂抗体（aPL）IgG 的一致性随着替代阈值的提高而提高。基于 ELISA 的 40/80 阈值和其他系统的适应阈值，LR 增加了血栓性和产科 APS 的 aPL IgG，但不增加 IgM。
40/80 单位作为中/高阈值可用于 aCL/aβ2GPI IgG ELISA，但不适用于 CLIA 和 MFI。非 ELISA 平台的替代半定量阈值可以通过临床方法或使用单克隆抗体来确定。半定量报告 aPL IgM 对增加 APS 的概率影响较小。
