Institute of Laboratory Medicine, Kantonsspital Aarau AG, Aarau, Switzerland.
Division of Clinical Immunology, University Hospital Zürich, Zürich, Switzerland.
Clin Chem Lab Med. 2019 Oct 25;57(11):1777-1783. doi: 10.1515/cclm-2019-0261.
Background The quantification of serum IgG4 is commonly performed during the diagnostic workup of IgG4-related diseases (IgG4-RD). According to recent literature, IgG4 values above 1.35 g/L are characteristic of IgG4-RD and support its diagnosis at initial presentation. The purpose of this study was to evaluate comparability and accuracy of the two main commercially available IgG4 assays (Siemens Healthineers and The Binding Site). Methods Method comparison was performed for IgG and IgG subclasses using a collective of selected samples with elevated serum IgG4. In addition, we assessed the accuracy of both assays using purified polyclonal and monoclonal IgG4 preparations. Results Our data show significant discrepancies between the two IgG subclass assays for the measurement of IgG4 and, to a lesser extent, IgG3. Conclusions The lack of standardization between the two main providers of commercially available IgG4 assays leads to significant inter-assay result discrepancies, which might potentially cause unnecessary clinical workup. We conclude that serum IgG4 assay-specific decision limits, and not an assay-independent single cut-off level for IgG4 (e.g. 1.35 g/L), should be used when assessing patients for IgG4-RD. An internationally recognized, certified reference material for IgG subclasses is urgently needed, and assay manufactures are encouraged to undertake steps toward standardization of measurements of IgG4 and other IgG subclasses.
在 IgG4 相关疾病（IgG4-RD）的诊断过程中，常进行血清 IgG4 的定量检测。根据最近的文献，IgG4 值高于 1.35 g/L 是 IgG4-RD 的特征，并支持其初始表现时的诊断。本研究旨在评估两种主要的商业 IgG4 检测方法（西门子和 The Binding Site）的可比性和准确性。
使用选定的具有升高的血清 IgG4 的样本集合，对 IgG 和 IgG 亚类进行方法比较。此外，我们使用纯化的多克隆和单克隆 IgG4 制剂评估了两种检测方法的准确性。
我们的数据显示，两种 IgG 亚类检测方法在测量 IgG4 时存在显著差异，在测量 IgG3 时差异较小。
两种主要商业 IgG4 检测方法之间缺乏标准化，导致检测结果存在显著差异，这可能导致不必要的临床检查。我们得出结论，在评估 IgG4-RD 患者时，应使用特定于血清 IgG4 检测方法的决策限值，而不是独立于检测方法的单一 IgG4 截断值（例如 1.35 g/L）。迫切需要一种国际认可的、经过认证的 IgG 亚类参考物质，并且鼓励检测制造商采取措施实现 IgG4 和其他 IgG 亚类测量的标准化。
