From the CHRU-Nancy, Department of Clinical Pharmacology and Toxicology - Centre Régional de Pharmacovigilance de Lorraine, Nancy, France.
Université de Lorraine, CHRU-Nancy, Department of Biochemistry, Nancy, France.
Endocr Pract. 2020 Sep;26(9):1031-1038. doi: 10.4158/EP-2020-0053.
Intravenous and subcutaneous immunoglobulins are commonly used for immune substitution or as immune modulators in a variety of inflammatory and autoimmune disorders. Exogenous thyroid-specific thyroglobulin (Tg) antibodies present in the donor plasma may interfere with the interpretation of measurements of Tg autoantibodies (Tg-Abs) in the recipient's plasma and potentially trigger an immune response in the recipient's immune cells. Levels of antibodies causing bioassay interferences or those leading to clinically relevant changes in patient outcomes are not known. Tg is used as a biomarker in the long-term surveillance of patients with differentiated thyroid cancer (DTC) following total thyroidectomy and radioactive iodine ablation. However, the presence of Tg-Abs in the circulation interferes with Tg measurements. Assessment of levels of Tg-Abs is thus recommended as a part of standard follow-up of DTC together with Tg testing.
To understand the potential mechanisms and pathophysiologic significance of possible interferences associated with administration immunoglobulin preparations and Tg measurement, we overview the current knowledge on interactions between Tg autoimmunity and immunoglobulin preparations and illustrate diagnostic challenges and perspectives for follow-up of patients with DTC treated with exogenous immunoglobulins.
In patients with DTC treated with immunoglobulin preparations, monitoring of thyroid cancer using Tg and Tg-Abs is challenging due to possible analytical interferences through passive transfer of exogenous antibodies from immunoglobulin preparations.
Analytical interferences must be suspected when a discrepancy exists between clinical examination and diagnostic tests. Collaboration between endocrinologists, biologists, and pharmacologists is fundamental to avoid misdiagnosis and unnecessary medical or radiologic procedures.
CT = computed tomography; DTC = differentiated thyroid cancer; FNAB = fine-needle aspiration biopsy; HAb = heterophile antibody; IMA = immunometric assay; IVIg = intravenous immunoglobulin; RAI = radioactive iodine; RIA = radioimmunoassay; SCIg = subcutaneous immunoglobulin; Tg = thyroglobulin; Tg-Ab = thyroglobulin autoantibody; Tg-MS = thyroglobulin mass spectrometry; TPO-Ab = thyroid peroxidase autoantibody; TSHR-Ab = thyrotropin receptor autoantibody.
静脉注射和皮下免疫球蛋白常用于替代免疫或作为各种炎症和自身免疫性疾病的免疫调节剂。供体血浆中存在的外源性甲状腺特异性甲状腺球蛋白（Tg）抗体可能会干扰受者血浆中 Tg 自身抗体（Tg-Ab）的测定，并可能在受者的免疫细胞中引发免疫反应。导致生物测定干扰的抗体水平或导致患者结局发生临床相关变化的抗体水平尚不清楚。Tg 作为分化型甲状腺癌（DTC）患者甲状腺全切和放射性碘消融后长期监测的生物标志物。然而，循环中的 Tg-Ab 会干扰 Tg 的测定。因此，建议在 DTC 标准随访中与 Tg 检测一起评估 Tg-Ab 水平。
为了了解与免疫球蛋白制剂给药和 Tg 测定相关的可能干扰的潜在机制和病理生理意义，我们综述了 Tg 自身免疫与免疫球蛋白制剂相互作用的现有知识，并举例说明了接受外源性免疫球蛋白治疗的 DTC 患者随访的诊断挑战和前景。
在接受免疫球蛋白制剂治疗的 DTC 患者中，由于免疫球蛋白制剂中外源抗体的被动转移可能导致分析干扰，因此使用 Tg 和 Tg-Ab 监测甲状腺癌具有挑战性。
当临床检查和诊断测试之间存在差异时，必须怀疑存在分析干扰。内分泌学家、生物学家和药理学家之间的合作对于避免误诊和不必要的医疗或放射程序至关重要。
CT = 计算机断层扫描；DTC = 分化型甲状腺癌；FNAB = 细针抽吸活检；HAb = 异嗜性抗体；IMA = 免疫测定法；IVIg = 静脉内免疫球蛋白；RAI = 放射性碘；RIA = 放射免疫测定；SCIg = 皮下免疫球蛋白；Tg = 甲状腺球蛋白；Tg-Ab = 甲状腺球蛋白自身抗体；Tg-MS = 甲状腺球蛋白质谱法；TPO-Ab = 甲状腺过氧化物酶自身抗体；TSHR-Ab = 促甲状腺激素受体自身抗体。
