First trimester screening for trisomy 21 in gestational week 8-10 by ADAM12-S as a maternal serum marker

<p>Abstract</p> <p>Background</p> <p>A disintegrin and metalloprotease 12 (ADAM12-S) has previously been reported to be significantly reduced in maternal serum from women with fetal aneuploidy early in the first trimester and to significantly improve the quality of risk assessment for fetal trisomy 21 in prenatal screening. The aim of this study was to determine whether ADAM12-S is a useful serum marker for fetal trisomy 21 using the mixture model.</p> <p>Method</p> <p>In this case control study ADAM12-S was measured by KRYPTOR ADAM12-S immunoassay in maternal serum from gestational weeks 8 to 11 in 46 samples of fetal trisomy 21 and in 645 controls. Comparison of sensitivity and specificity of first trimester screening for fetal trisomy 21 with or without ADAM12-S included in the risk assessment using the mixture model.</p> <p>Results</p> <p>The concentration of ADAM12-S increased from week 8 to 11 and was negatively correlated with maternal weight. Log MoM ADAM12-S was positively correlated with log MoM PAPP-A (r = 0.39, P < 0.001), and with log MoM free beta hCG (r = 0.21, P < 0.001). The median ADAM12-S MoM in cases of fetal trisomy 21 in gestational week 8 was 0.66 increasing to approx. 0.9 MoM in week 9 and 10. The use of ADAM12-S along with biochemical markers from the combined test (PAPP-A, free beta hCG) with or without nuchal translucency measurement did not affect the detection rate or false positive rate of fetal aneuploidy as compared to routine screening using PAPP-A and free β-hCG with or without nuchal translucency.</p> <p>Conclusion</p> <p>The data show moderately decreased levels of ADAM12-S in cases of fetal aneuploidy in gestational weeks 8-11. However, including ADAM12-S in the routine risk does not improve the performance of first trimester screening for fetal trisomy 21.</p

Maternal serum placental growth factor (PlGF) isoforms 1 and 2 at 11-13, 20-24 and 30-34 weeks’ gestation in late onset preeclampsia and small for gestational age neonates

&lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; To compare the maternal serum concentrations of placental growth factor (PlGF)-1 and PlGF-2 in the first, second and third trimesters in normal pregnancies and in those complicated by pre-eclampsia (PE) or the delivery of small for gestational age (SGA) neonates after 37 weeks. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Serum PlGF-1 and PlGF-2 were measured at 11-13, 20-24 and 30-34 weeks' gestation in 50 cases of PE, 99 cases of SGA and 298 controls. The values of PlGF-1 and PlGF-2 at 11-13 weeks were expressed as multiples of the median (MoM) after adjustment for maternal characteristics. The distributions of PlGF-1 and PlGF-2 in cases and controls at 20-24 and 30-34 weeks were converted to MoM of the values at 11-13 weeks and compared. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Serum PlGF-1 and PlGF-2 levels were highly correlated and both increased with gestational age. At 30-34 weeks, the median MoM values for PlGF-1 and PlGF-2 in the late PE (4.2 and 4.3) and late SGA (7.2 and 6.0) groups were significantly lower than in the controls (12.8 and 9.9). Combining the two isoforms did not improve the prediction of late PE and late SGA provided by PlGF-1 alone. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; The performances of serum PlGF-1 and PlGF-2 in the prediction of late PE and late SGA are similar.</jats:p

A Descriptive Model for the Kinetics of a Homogeneous Fluorometric Immunoassay

International audienc

Serum Matrix Metalloproteinase-7 is an independent prognostic biomarker in advanced bladder cancer

International audienceBACKGROUND: Urine markers have been studied extensively but there is a lack of blood prognostic markers in bladder cancer. MMP-7 is produced by stromal cells and by tumor cells and is overexpressed in a variety of epithelial and mesenchymal tumors. In this study, we assessed with an immunoassay we developed, the prognostic value of serum MMP-7 in a series of patients with advanced bladder cancer. METHODS: Serum samples were collected from 56 patients with advanced bladder cancer who were treated at the Montpellier Cancer Institute between March 2003 and December 2004. MMP-7 was quantified in serum samples by using a homogeneous sandwich fluoroimmunoassay we developed based on the time resolved amplified cryptate emission (TRACE) technology. RESULTS: The median overall survival of the study population was 2.2 years (95% CI, 1.4 to 3.0) with 1- and 5-year survival rates of 73% (95% CI, 59% to 82%) and 25% (95% CI, 14% to 37%), respectively. High MMP-7 serum levels were associated with poor survival. Using a cut-off value of 11.5 ng/mL, the median overall survival was 3.0 years (95% CI, 1.5 to 5.1) for patients with MMP-7 serum level \textless11.5 ng/mL and 1.3 years (95% CI, 0.8 to 2.5) for patients with serum level ?11.5 ng/mL. Multivariate analysis identified high MMP-7 serum concentration as an independent prognostic factor for survival in patients with advanced bladder cancer (R?=?2.1, 95% CI, 1.1 to 4.4). CONCLUSIONS: Our results show that the MMP-7 serum concentration is an independent prognostic factor in patients with locally advanced and or metastatic bladder cancer

Rapid development of sensitive, high-throughput, quantitative and highly selective mass spectrometric targeted immunoassays for clinically important proteins in human plasma and serum

OBJECTIVES: The aim of this study was to develop high-throughput, quantitative and highly selective mass spectrometric, targeted immunoassays for clinically important proteins in human plasma or serum. DESIGN AND METHODS: The described method coupled mass spectrometric immunoassay (MSIA), a previously developed technique for immunoenrichment on a monolithic microcolumn activated with an anti-protein antibody and fixed in a pipette tip, to selected reaction monitoring (SRM) detection and accurate quantification of targeted peptides, including clinically relevant sequence or truncated variants. RESULTS: In this report, we demonstrate the rapid development of MSIA-SRM assays for sixteen different target proteins spanning seven different clinically important areas (including neurological, Alzheimer's, cardiovascular, endocrine function, cancer and other diseases) and ranging in concentration from pg/mL to mg/mL. The reported MSIA-SRM assays demonstrated high sensitivity (within published clinical ranges), precision, robustness and high-throughput as well as specific detection of clinically relevant isoforms for many of the target proteins. Most of the assays were tested with bona-fide clinical samples. In addition, positive correlations, (R2 0.67–0.87, depending on the target peptide), were demonstrated for MSIA-SRM assay data with clinical analyzer measurements of parathyroid hormone (PTH) and insulin growth factor 1 (IGF1) in clinical sample cohorts. CONCLUSIONS: We have presented a practical and scalable method for rapid development and deployment of MS-based SRM assays for clinically relevant proteins and measured levels of the target analytes in bona fide clinical samples. The method permits the specific quantification of individual protein isoforms and addresses the difficult problem of protein heterogeneity in clinical proteomics applications