Total pregnancy‐associated plasma protein A—a first trimester maternal serum marker for Down's syndrome: clinical and technical assessment of a poly‐monoclonal enzyme immunoassay

Abstract

Pregnancy‐associated plasma protein A (PAPP‐A) is a maternal serum marker of fetal chromosomal disease and a risk marker for adverse outcome. PAPP‐A in the circulation exists both as a 2:2 complex (PAPP‐A/proMBP) with the proform of eosinophil major basic protein (proMBP) and as dimeric PAPP‐A. Non‐PAPP‐A containing proMBP complexes constitute the bulk of proMBP in maternal serum. We developed and characterized a sandwich enzyme immunoassay for PAPP‐A using a polyclonal rabbit anti‐PAPP‐A/proMBP antibody (SSI 6823) and a monoclonal murine anti‐PAPP‐A/proMBP antibody (HYB 234‐3), reactive with the PAPP‐A part of PAPP‐A/proMBP. The assay range was 2 mIU/L–500 mIU/L, intra‐ and inter‐assay coefficients of variation <10%. The immunoreactivity eluted ahead of thyroglobulin, M_r 669 kDa, in gel filtration and bound to a heparin column. Serum concentrations of PAPP‐A were determined in gestational weeks 5–13 in 167 pregnant women with normal fetuses and 39 women with Down's syndrome (DS) fetuses. The median PAPP‐A MoM (multiples of the median in normal controls) in DS pregnancies was 0.30 (quartile range: 0.17–0.54). The PAPP‐A logMoMs in DS pregnancies were normally distributed with a mean of −0.5927 and SD of 0.3639. When simulating the performance of PAPP‐A and age as markers for DS in population screening a detection rate (DR) of 62% was found for a screen positive rate (SPR) of 5%. Together with β‐HCG and nuchal translucency, two other first trimester markers for fetal DS, a DR 90% could be obtained for an SPR of 5%.

• eosinophil major basic protein
• pregnancy‐associated plasma protein A
• pregnancy proteins
• prenatal screening
• trisomy 21