title: Pregnancy associated plasma protein-A2: a novel biomarker for Down syndrome.
abstract: BACKGROUND
  In an effort to improve prenatal screening for Trisomy 21, we evaluated pregnancy associated plasma protein-A2 (PAPP-A2) as a potential novel second trimester biomarker for Trisomy 21.
  
  
  METHODS
  Trisomy 21 and normal control mid-trimester placental samples were subjected to quantitative rt PCR analysis of seven genes we had previously found to be differentially expressed in Trisomy 21 placentae. The localization and differential expression of PAPP-A2 in second trimester placentae from normal and Trisomy 21 pregnancies was determined by immunohistochemistry. PAPP-A2 maternal serum protein levels in ten Trisomy 21 and ten diploid pregnancies were compared by Western blotting. Maternal serum PAPP-A2 levels were measured in 30 Down syndrome cases and 142 normal controls, using ELISA. Regression analysis was used to determine the correlation of PAPP-A2 with other existing markers of Trisomy 21.
  
  
  RESULTS
  PAPP-A2 (aka PLAC 3) mRNA and protein expression were both increased in Down syndrome placentae as compared to diploid placentae. PAPP-A2 was also increased in maternal serum from Down syndrome pregnancies as compared to diploid pregnancies. PAPP-A2 expression correlated weakly with established markers.
  
  
  CONCLUSIONS
  This work takes advantage of our previously performed systematic approach to the discovery of novel maternal serum biomarkers for Trisomy 21, using cDNA microarray analysis. Beginning with the validation of the microarray results, we have tracked PAPP-A2 overexpression in Down syndrome from placental mRNA to maternal serum protein.
  
  
  CONCLUSIONS
  PAPP-A2 could serve as an additional maternal serum marker in prenatal screening for Trisomy 21.
authors.affiliation: Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Munnangi
authors.affiliation: Natera, San Carlos, CA, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Gross
authors.affiliation: Department of Obstetrics and Gynecology, North Shore-LIJ Health System, Glen Cove, NY, USA.
authors.forename: R
authors.initials: R
authors.lastname: Madankumar
authors.affiliation: Endoclab, Porto, Portugal.
authors.forename: G
authors.initials: G
authors.lastname: Salcedo
authors.affiliation: Department of Pharmaceutical Sciences, St. John's University, Queens, NY, USA; Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, USA; Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY, USA. Electronic address: rezniks@stjohns.edu.
authors.forename: S E
authors.initials: SE
authors.lastname: Reznik
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D004314:Down Syndrome / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006801:Humans; D062145:Maternal Serum Screening Tests; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D015415:Biomarkers; C430889:PAPPA2 protein, human; D011266:Pregnancy-Associated Plasma Protein-A
keywords: Biomarker; Down syndrome; Maternal serum; Placenta; Pregnancy associated plasma protein-A2; Second trimester