PAPP‐A and IGFBP‐4 in Abmormal Pregnancy Sera

Insulin‐like Growth Factor Binding Protein‐4 (IGFBP‐4) regulates the activity of Insulin‐like Growth Factor‐I. IGFBP‐4 is proteolytically regulated by Pregnancy‐Associated Plasma Protein‐A (PAPP‐A). PAPP‐A serum concentrations are decreased in pregnancies carrying fetuses with extra chromosomes (trisomies). We have hypothesized that (1) lowered PAPP‐A levels in abnormal pregnancy sera may arise from the effects of structural changes in PAPP‐A and (2) concentrations of IGFBP‐4 in pregnancy serum may correlate with PAPP‐A levels. Results are reported for (a) ELISA measurement of paired PAPP‐A and IGFBP‐4 values in normal and abnormal pregnancy sera and (b) Western blotting analysis of sera by using monoclonal antibodies to PAPP‐A's MBP subunit. For 13 different pregnancy sera involving fetal trisomies, 10 normal pregnancy sera and 8 non‐pregnancy sera, IGFBP‐4 were not inversely related to PAPP‐A. The MBP subunit of PAPP‐A was detected in 3/4 normal pregnancy sera, 0/3 sera involving trisomies and 0/1 non‐pregnancy sera. Although IGFBP‐4 is one of only two known substrates for PAPP‐A protease, pregnancy sera IGFBP‐4 concentrations were not inversely correlated with those of PAPP‐A. Studies need to be performed with larger numbers of sera to see if these observations hold. Supported by an award from the ASU Office of Research from NIH Grant no: 5P20M0001085‐03