Double-monoclonal immunofluorometric assays for pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/proMBP) complex in first-trimester maternal serum screening for Down syndrome.

Four double-monoclonal time-resolved immunofluorometric assays (TrIFMAs) have been developed for the specific determination of pregnancy-associated plasma protein A/proeosinophil major basic protein (PAPP-A/ proMBP) complex in first-trimester maternal serum samples. The assays have a functional sensitivity of < 4 mIU/L and a working range from 4 to 1000 mIU/L. These 4 assays, together with a polyclonal sandwich TrIFMA, were compared for their ability to discriminate between normal pregnancies (n = 149) and pregnancies carrying a Down syndrome fetus (n = 36) in maternal serum screening samples from gestational weeks 4-13. In 26 Down syndrome pregnancies from gestational weeks 7-12, the median PAPP-A multiples of the median concentration in controls (MoMs) determined by monoclonal antibody combinations 234-3/234-2*, 234-4/234-2*, 234-4/234-5*, and 234-5/234-6* were 0.35, 0.37, 0.42, and 0.44, respectively, whereas the median MoM determined by the polyclonal assay was 0.56. ROC curve analysis also showed that better overall diagnostic accuracy and detection rates were achieved by the monoclonal TrIFMAs than by the polyclonal TrIFMA. This report is the first to describe assays that specifically measure PAPP-A/proMBP complex without possible interference from other proMBP-containing complexes.