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 (TrIFMA s) have been developed for the specific determination of pregnancy-ass ociated plasma protein A/proeosinophil major basic protein (PAPP-A/ pr oMBP) complex in first-trimester maternal serum samples. The assays ha ve 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 pregn ancies (n = 149) and pregnancies carrying a Down syndrome fetus (n = 3 6) 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) determ ined by monoclonal antibody combinations 234-3/234-2, 234-4/234-2*, 2 34-4/234-5, and 234-5/234-6* were 0.35, 0.37, 0.42, and 0.44, respect ively, whereas the median MoM determined by the polyclonal assay was 0 .56. ROC curve analysis also showed that better overall diagnostic acc uracy 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 inte rference from other proMBP-containing complexes.