Fisker S, Ebdrup L, Orskov H
Department of Endocrinology and Diabetes, University Hospital of Aarhus, Denmark.
Scand J Clin Lab Invest. 1998 Aug;58(5):373-81. doi: 10.1080/00365519850186355.
Growth hormone (GH) quantitation in biological fluids varies depending on the assays employed, and factors which may interfere in the assays include the high affinity GH-binding protein (GHBP). To evaluate this potential effect on GH estimates, we studied the influence of adding increasing amounts of high affinity glycosylated GHBP to normal, acromegalic and GH-deficient sera, which were then processed in four different immunoassays. Two commercial immunometric assays, Delfia and Nichols (assays 1 and 2), and two RIAs, one using a polyethylene glycol (PEG) precipitation (assay 3) and one using wick-chromatography (assay 4) for separation of free and bound 125I-GH, were employed. In the Delfia assays, GH estimates of 11 sera decreased (p < 0.05) to 87.2 +/- 2.6%, 73.0 +/- 2.7% and 60.1 +/- 2.5% (mean +/- SEM) of basal GH estimates with the addition of GHBP in concentrations of 0.54, 2.14 and 6.42 nmol/l, respectively. In the Nichols assay, GH estimates were not significantly reduced (93.4 +/- 2.6%, 83.8 +/- 4.5% and 83.9 +/- 3.9%) with the applied GHBP concentrations. In assay 3 (RIA), the addition of GHBP increased GH estimates to 122 +/- 10.0% and 167 +/- 19.1% (both p < 0.05) with the addition of GHBP in concentrations of 2.14 and 6.42 nmol/l, respectively, whereas an increase in GHBP concentration of 0.54 nmol/l did not change the estimates from basal levels (99.0 +/- 4.8%, p > 0.05). In assay 4 (RIA), the addition of GHBP induced decreased GH estimates. With this varying influence of GHBP on GH estimates, binding protein interference should be taken into consideration when comparing GH estimates obtained with many currently utilized GH immunoassays. The present results demonstrate that GHBP levels within physiological range may interfere with the results of GH assays, giving either spuriously high or low values depending on the GH assay methodology.
生物体液中生长激素(GH)的定量测定结果因所采用的检测方法而异,可能干扰检测的因素包括高亲和力生长激素结合蛋白(GHBP)。为评估其对GH测定值的潜在影响,我们研究了向正常血清、肢端肥大症患者血清和生长激素缺乏症患者血清中添加不同量高亲和力糖基化GHBP的影响,随后用四种不同的免疫测定方法对这些血清进行处理。采用了两种商业免疫测定法,即Delfia法和Nichols法(检测方法1和2),以及两种放射免疫分析法(RIA),一种使用聚乙二醇(PEG)沉淀法(检测方法3),另一种使用灯芯色谱法(检测方法4)来分离游离的和结合的125I-GH。在Delfia检测法中,添加浓度分别为0.54、2.14和6.42 nmol/l的GHBP后,11份血清的GH测定值分别降至基础GH测定值的87.2±2.6%、73.0±2.7%和60.1±2.5%(平均值±标准误)(p<0.05)。在Nichols检测法中,在所应用的GHBP浓度下,GH测定值未显著降低(分别为93.4±2.6%、83.8±4.5%和83.9±3.9%)。在检测方法3(RIA)中,添加浓度为2.14和6.42 nmol/l的GHBP后,GH测定值分别增加至122±10.0%和167±19.1%(均p<0.05),而添加浓度为0.54 nmol/l的GHBP时,测定值与基础水平相比未发生变化(99.0±4.8%,p>0.05)。在检测方法4(RIA)中,添加GHBP导致GH测定值降低。鉴于GHBP对GH测定值有这种不同的影响,在比较目前许多GH免疫测定法所获得的GH测定值时,应考虑结合蛋白的干扰。目前的结果表明,生理范围内的GHBP水平可能会干扰GH检测结果,根据GH检测方法的不同,可能会给出假性的高值或低值。