Dept of Laboratory medicine, Ghent University.
Acta Clin Belg. 2022 Feb;77(1):204-210. doi: 10.1080/17843286.2020.1780770. Epub 2020 Jun 20.
Biotin supplementation (mainly OTC preparations) has gained popularity. There are concerns about biotin interference in immunoassays and potential misdiagnosis, especially since the discovery of high dose therapy in MS. This review summarizes the dangers of biotin usage and possible countermeasures.
Immunoassays design determines whether positive or negative analytical errors may occur. Techniques using biotinylated reagent and biotin binding proteins may generate errors. In sandwich immunoassays, biotin causes lowered results. Competitive immunoassays are more vulnerable: biotin usage causes false increased results. The interference is platform dependent. Parameters vary in their susceptibility: a combination of false positives and negatives mimicking a coherent profile is dangerous, e.g. combining falsely lowered TSH with falsely elevated FT4/FT3 mimicking hyperthyreosis. Other susceptible parameters are thyroglobulin, DHEA-S, estradiol, testosterone, ferritin, progesterone, Vitamin D, Vitamin B12, PSA, PTH, LH, FSH, Troponins I and T, Pro-BNP. Digoxin and PSA may also be affected. Tumor markers and ß-hCG are robust. Inserts of serological markers of HIV, hepatitis B and C warn for biotin interference.
Manufacturers have made assays less vulnerable for biotin interference. In doubtful cases, it is helpful to determine testosterone in females and estrogen in males. Both are elevated if biotin interference is present. Biotin supplementation should be discontinued. However, this is impossible in MS patients needing biotin, as interrupting this medication is discouraged.
Solutions to overcome this interference are: informing patients prior to analysis (avoiding peak biotin values when sampling), choice of appropriate immunoassays, and use of biotin removing steps prior to analysis.
生物素补充剂(主要是 OTC 制剂)已广受欢迎。人们担心生物素会干扰免疫分析并导致潜在的误诊,尤其是在多发性硬化症中发现高剂量治疗之后。本文综述了生物素使用的危险和可能的对策。
免疫分析的设计决定了是否可能出现阳性或阴性的分析错误。使用生物素化试剂和生物素结合蛋白的技术可能会产生错误。在夹心免疫分析中,生物素会导致结果降低。竞争免疫分析更容易受到影响:生物素的使用会导致错误的结果升高。这种干扰依赖于平台。各种参数的易感性不同:假阳性和假阴性的组合会模仿一致的特征,例如结合假性降低的 TSH 和假性升高的 FT4/FT3 来模拟甲状腺功能亢进。其他易受影响的参数包括甲状腺球蛋白、DHEA-S、雌二醇、睾酮、铁蛋白、孕酮、维生素 D、维生素 B12、PSA、PTH、LH、FSH、肌钙蛋白 I 和 T、Pro-BNP。地高辛和 PSA 也可能受到影响。肿瘤标志物和β-hCG 则较为稳健。插入 HIV、乙型肝炎和丙型肝炎的血清学标志物可预警生物素干扰。
制造商已经使检测对生物素干扰的敏感性降低。在可疑的情况下,确定女性的睾酮和男性的雌激素水平会有所帮助。如果存在生物素干扰,两者都会升高。应停止补充生物素。但是,对于需要生物素的多发性硬化症患者来说,这是不可能的,因为中断这种药物治疗是不被鼓励的。
克服这种干扰的方法是:在分析前告知患者(避免在采样时达到生物素峰值),选择适当的免疫分析方法,并在分析前使用去除生物素的步骤。