Pregnancy Associated Plasma Protein-A2: A Novel Biomarker For Down Syndrome
Swapna Munnangi, Rajeevi Madankumar, Meghna Alimchandani, Ashley Varghese, Susan J. Gross and Sandra E. Reznik, College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences
Abstract: Down’s syndrome, or Trisomy 21, is the most common human chromosomal disorder. There is a need to improve the sensitivity and specificity of current screening methods to identify pregnancies at high risk of Down’s syndrome (DS). In an effort to supplement the existing maternal serum markers for DS, in the current work we evaluate the clinical utility of pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for aneuploidy. In previous microarray studies on normal and DS placental tissue, we have found that the PAPP-A2 gene is differentially up-regulated in DS pregnancies by more than two-fold. In the current work, greater than two-fold up-regulation of placental PAPP-A2 in T21 is confirmed by quantitative rt pcr. Moreover, we analyze the levels of PAPP-A2 in maternal serum from Down's syndrome (DS) pregnancies using Western blotting technique and find that in DS pregnancies, median PAPP-A2 levels are significantly elevated to 2.69 multiples of the median (MoM) (P<0.05) in maternal serum, when compared with uncomplicated pregnancies. Immunohistochemistry studies reveal that PAPP-A2 is mainly localized to the trophoblastic layer of chorinionic villi. Semi-quantitative studies of staining intensity reveal a trend towards stronger staining of placental trophoblasts of DS tissues. These results support the idea that maternal serum levels of PAPP-A2 are elevated due to increased production in the placenta, and increased immunostaining of trophoblasts suggests that this may be due to increased production in the trophoblasts. ELISA based immunoassay on a larger population is in progress to further test our hypothesis that PAPP-A2 can serve as an additional biomarker for screening pregnancies for Down’s syndrome.