Abe Masaki, Matsuura Tomokazu, Hyoki Miyuki, Abe Ikurou, Tanigawa Keishi, Kaito Ken
Central Clinical Laboratory, Jikei University Hospital, Minato ku, Tokyo, Japan.
Rinsho Byori. 2011 Aug;59(8):763-9.
False positive elevation of carcinoembryonic antigen (CEA) was observed in a 65-year-old woman who was treated with dendritic cell therapy (DCT) and activated lymphocyte therapy (ALT) for intrahepatic cholangiocarcinoma. Three months after the initiation of these therapies, her CEA value measured by AIA (TOSOH) began to increase without any evidence of worsening of cholangiocarcinoma. CEA was measured by several different methods, and only the result measured by AIA was high, indicating the presence of a false positive phenomenon. To clarify this phenomenon, we evaluated the patient's serum precisely. Gel filtration chromatography of her serum showed that CEA was detected in the elution fraction of IgG, which was different from the reference samples. Furthermore, this peak disappeared after incubation of patient's CEA and HBR-1. The immunoglobulin absorption test revealed that CEA value was decreased only after absorption of IgG and absorption tests using HBR-1 and MAK-absorbents showed a dramatic decrease in CEA value. These findings indicated the presence of IgG type human anti-mouse antibodies (HAMA), which interfered the measurement by AIA. Although we could not identify the reason why HAMA was produced in this patient, the facts that the false positive phenomenon was observed after the initiation of DCT and ALT, and that CEA value decreased after theses therapies were discontinued, indicated that immuno-modulaton by DCT and ALT may have a close relationship to HAMA production. It was probable that DCT and ALT activated preexisting heterophile-antibody-producing cells, which stimulated HAMA production. The incidence of such false positive reaction of CEA by HAMA in patients with DCT and ALT was low, but as the number of the patient with immuno-cell therapy increases, the incidence of such phenomenon surely increases. Because HAMA reacts to all types of immunoassay, careful attention should be paid to the evaluation of laboratory findings in patients undergoing with such immuno-cell therapies.
一名65岁女性因肝内胆管癌接受树突状细胞疗法（DCT）和活化淋巴细胞疗法（ALT）治疗，期间癌胚抗原（CEA）出现假阳性升高。在开始这些治疗三个月后，她通过AIA（东芝）检测的CEA值开始升高，而此时并无胆管癌病情恶化的迹象。CEA通过几种不同方法进行检测，只有AIA检测的结果偏高，表明存在假阳性现象。为了阐明这一现象，我们对患者血清进行了精确评估。对其血清进行凝胶过滤色谱分析显示，在IgG洗脱部分检测到了CEA，这与参考样本不同。此外，患者的CEA与HBR-1孵育后，该峰消失。免疫球蛋白吸收试验表明，仅在吸收IgG后CEA值降低，而使用HBR-1和MAK吸附剂的吸收试验显示CEA值显著降低。这些发现表明存在IgG型人抗鼠抗体（HAMA），它干扰了AIA检测。虽然我们无法确定该患者产生HAMA的原因，但在开始DCT和ALT后观察到假阳性现象，以及在停止这些治疗后CEA值降低这一事实，表明DCT和ALT引起的免疫调节可能与HAMA产生密切相关。很可能是DCT和ALT激活了预先存在的产生嗜异性抗体的细胞，从而刺激了HAMA的产生。在接受DCT和ALT治疗的患者中，由HAMA导致的CEA这种假阳性反应发生率较低，但随着接受免疫细胞治疗的患者数量增加，这种现象的发生率肯定会上升。由于HAMA会与所有类型的免疫测定发生反应，因此对于接受此类免疫细胞治疗的患者，在评估实验室检查结果时应格外小心。
