Akamine Yumiko, Kagaya Hideaki, Ohkubo Tadashi, Satoh Shigeru, Miura Masatomo
Department of Pharmacy, Akita University Hospital, Akita, Japan.
Research Institute of Shichifuku Pharmacy, Aomori, Japan.
J Clin Pharm Ther. 2018 Apr;43(2):181-188. doi: 10.1111/jcpt.12624. Epub 2017 Sep 10.
The anti-tacrolimus antibodies used in commercial immunoassay methods have cross-reactivity with tacrolimus metabolites. The aim of this study was to investigate differences in the effects of CYP3A5 polymorphism on tacrolimus concentrations obtained by four immunoassay methods in renal transplant patients.
Samples (n = 508) were evaluated using four immunoassays (chemiluminescence enzyme immunoassay [CLIA], affinity column-mediated immunoassay [ACMIA], electrochemiluminescence immunoassay [ECLIA] and latex agglutination turbidimetric immunoassay [LTIA]).
Bland-Altman plots showed average biases of -0.12 (±1.96 SD: -1.30-1.05) ng/mL for CLIA, -0.30 (-1.59-1.00) ng/mL for ECLIA, 0.42 (-1.21-2.05) ng/mL for ACMIA and 1.88 (-0.51-4.28) ng/mL for LTIA, when considering the mean of the three immunoassays (CLIA, ECLIA and ACMIA). In multiple regression analysis, the difference (CLIA-mean) was affected by haematocrit levels. Differences in ECLIA were correlated with red blood cell counts. For LTIA, CYP3A5 genotype and haematocrit levels were identified as independent predictors for this bias.
The results obtained by CLIA, ECLIA and ACMIA were not affected by CYP3A5 polymorphism. However, in LTIA, CYP3A5*1/3-derived data exhibited an inverse relationship in Bland-Altman analysis (slope: -0.0824). Higher cross-reactivity with 12-hydroxy tacrolimus at lower concentrations may occur in patients with the CYP3A51/3 genotype. Because patients with the CYP3A51 allele identified using LTIA may show higher blood concentrations of tacrolimus at lower target concentrations, for example 3.0 ng/mL, compared with other immunoassay methods, there is a need for sufficient consideration of the interpretation of values measured by LTIA.
商业免疫分析方法中使用的抗他克莫司抗体与他克莫司代谢产物存在交叉反应。本研究旨在探讨CYP3A5基因多态性对肾移植患者通过四种免疫分析方法测得的他克莫司浓度的影响差异。
使用四种免疫分析方法（化学发光酶免疫分析[CLIA]、亲和柱介导免疫分析[ACMIA]、电化学发光免疫分析[ECLIA]和乳胶凝集比浊免疫分析[LTIA]）对508份样本进行评估。
采用布兰德-奥特曼图分析，以CLIA、ECLIA和ACMIA三种免疫分析方法的均值为参照，CLIA的平均偏差为-0.12（±1.96标准差：-1.30至1.05）ng/mL，ECLIA为-0.30（-1.59至1.00）ng/mL，ACMIA为0.42（-1.21至2.05）ng/mL，LTIA为1.88（-0.51至4.28）ng/mL。在多元回归分析中，（CLIA-均值）差异受血细胞比容水平影响。ECLIA的差异与红细胞计数相关。对于LTIA，CYP3A5基因型和血细胞比容水平被确定为该偏差的独立预测因素。
CLIA、ECLIA和ACMIA获得的结果不受CYP3A5基因多态性影响。然而，在LTIA中，CYP3A5*1/3衍生数据在布兰德-奥特曼分析中呈现负相关关系（斜率：-0.0824）。CYP3A51/3基因型患者在较低浓度下可能与12-羟基他克莫司有更高的交叉反应。由于使用LTIA鉴定出携带CYP3A51等位基因的患者在较低目标浓度（例如3.0 ng/mL）下可能显示出比其他免疫分析方法更高的他克莫司血药浓度，因此需要充分考虑对LTIA测得值的解读。
