Pregnancy-associated plasma protein A (PAPP-A): theoretical and clinical aspects.

Pregnancy-associated plasma protein A (PAPP-A) is an important pregnancy protein. PAPP-A exists in pregnancy serum as a heterotetrameric 2:2 complex with the proform of eosinophil major basic protein (proMBP), forming an approximately 500 kDa and called PAPP-A/proMBP. The gene of PAPP-A has been assigned to human chromosome 9q 33.1. PAPP-A belongs to the metzincin superfamily of metalloproteinases. It contains five short consensus repeats (SCR) and three the lin-notch repeats (LNR) and in addition a putative Zn binding site. The main site of both PAPP-A and proMBP synthesis during pregnancy is the placenta as shown by in situ hybridization. PAPP-A seems to be the predominating IGFBP-4 proteinase in pregnancy serum. In the women the levels of PAPP-A are highest during pregnancy, when plasma levels increase by a factor of about 150 as compared to the nonpregnant state. PAPP-A is the most abundant in the peripheral maternal circulation. Determination of PAPP-A in pregnancy serum has a limited value in some complication in gravidity such as a threatened abortion, ectopic gravidity, preeclampsia or diabetes mellitus. PAPP-A determination will gain increasing importance since this protein seems to be the major biochemical marker of Down syndrome in the first trimester of pregnancy. Maternal serum levels of PAPP-A in the first trimester are significantly reduced when a fetus affected by Down syndrome is present. Low first trimester maternal serum levels were found not only in trisomy 21 but also in non-Down syndrome fetal aneuploidies. Another contribution of PAPP-A determination may be in differentation of stable and unstable angina pectoris. (Tab. 3, Fig. 5, Ref. 78.)