Laigaard Jennie, Sørensen Tina, Fröhlich Camilla, Pedersen Bent Nørgaard, Christiansen Michael, Schiøtt Kirsten, Uldbjerg Niels, Albrechtsen Reidar, Clausen Helle V, Ottesen Bent, Wewer Ulla M
Department of Gynecology and Obstetrics, Rigshospitalet, University of Copenhagen, Denmark.
Prenat Diagn. 2003 Dec 30;23(13):1086-91. doi: 10.1002/pd.762.
The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health.
We developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration.
We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks, and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers.
ADAM12 is a promising marker for Down syndrome.
生物可利用的胰岛素样生长因子（IGF）Ⅰ和Ⅱ的浓度对胎儿生长很重要。它由胰岛素样生长因子结合蛋白（IGFBP）1至6调节。IGFBP - 3在人妊娠血清中会发生蛋白水解裂解；因此，IGFBP - 3血清水平在孕期会显著下降。ADAM12（一种解整合素和金属蛋白酶）是一种IGFBP - 3和IGFBP - 5蛋白酶，存在于人妊娠血清中。本研究的目的是确定母体血清中ADAM12的浓度是否是胎儿健康的有用指标。
我们开发了一种酶联免疫吸附测定（ELISA）法来定量血清中的ADAM12。测定范围为42至667μg/L。重组ADAM12用作校准标准品。
我们发现ADAM12在血清中高度稳定。血清浓度从妊娠第8周的180μg/L增加到16周时的670μg/L，并在足月时达到12000μg/L。在18例孕早期唐氏综合征妊娠中，ADAM12的浓度降低，因此平均倍数（MoM）值的中位数为0.14（0.01 - 0.76）。通过使用ADAM12和孕妇年龄作为筛查标志物的蒙特卡洛估计，发现当筛查阳性率为3.2%且风险截断值为1:400时，胎儿唐氏综合征的检出率为82%。
ADAM12是一种有前景的唐氏综合征标志物。
