Pregnancy-associated plasma protein-A

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Contents

Introduction

Prenatal diagnosis- novel serum biomarker screening

Pregnancy-associated plasma protein-A (PAPP-A) largest of the pregnancy associated proteins produced by both the embryo and the placenta (syncytiocytotrophoblasts) during pregnancy (Placenta Notes). This protein is thought to have several different functions, including preventing recognition of the fetus by the maternal immune system, matrix mineralization and angiogenesis. Levels of PAPP-A rise from first detection in the first trimester until term.

Detection of this protein is also suggested as a first and second trimester diagnostic test for aneuploidies, including Trisomy 21 or Down Syndrome.

Maternal serum concentrations are related to subsequent fetal growth and this relationship has suggested that it can be used as a diagnostic test for adverse pregnancy outcomes (intrauterine growth restriction, premature birth, preeclampsia, and stillbirth).

Alternative names: pappalysin 1, PAPP-A, PAPPA1, SP4, high molecular weight alpha-2 mobile pregnancy-specific protein, IGFBP4 protease (IGFBP-4ase), ASBABP2, DIPLA1, PAPA

Diagnosis Links: Prenatal Diagnosis | Pregnancy Test | Amniocentesis | Chorionic villus sampling | Ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis | Trisomy 21 | Original PAPP-A page

PAPP-A Levels

  • Levels of PAPP-A rise from initial detection at about 32 days after ovulation, then increasing rapidly (levels doubling every 3 days), finally continuing to rise more slowly until term.
  • Electroimmunoassays allow the detection as early as the fifth week of pregnancy, of circulating levels down to 10 microgram/L.
  • Adult male serum PAPP-A circulating level is 8.03±2.75 mIU/L (mean±SD).

Maternal serum level

  • increased PAPP-A indicate increased risk of trisomy 21
  • reduced PAPP-A associated with an increased risk of trisomy 18
  • First trimester low PAPP-A (< 0.4 MoM) associated with an increased frequency of adverse obstetrical outcomes.[1]

Protein

  • large zinc glycoprotein [2] [3]
  • secreted metalloproteinase (EC=3.4.24.79) which cleaves insulin-like growth factor binding proteins (IGFBPs).
    • specifically cleaves IGFBP-4 and IGFBP-5, releasing bound IGF
  • present in pregnancy serum
    • heterotetrameric 2:2 complex with proform of eosinophil major basic protein (proMBP).[4]
    • approximate 500 kDa complex called PAPP-A/proMBP.
  • placental origin
  • also in: ovarian follicles, follicular fluid, luteal cells
    • uterine tubes of nonpregnant women
    • seminal vesicles and seminal fluid of males

Links: OMIM | GeneCards | UniProtKB/Swiss-Prot

References

  1. Obstetrical complications associated with abnormal maternal serum markers analytes. Gagnon A, Wilson RD, Audibert F, Allen VM, Blight C, Brock JA, Désilets VA, Johnson JA, Langlois S, Summers A, Wyatt P; Society of Obstetricians and Gynaecologists of Canada Genetics Committee. J Obstet Gynaecol Can. 2008 Oct;30(10):918-49. Review. PMID: 19038077
  2. Amino acid sequence of human pregnancy-associated plasma protein-A derived from cloned cDNA. Kristensen T, Oxvig C, Sand O, Møller NP, Sottrup-Jensen L. Biochemistry. 1994 Feb 15;33(6):1592-8. PMID: 7508748
  3. Complete cDNA sequence of the preproform of human pregnancy-associated plasma protein-A. Evidence for expression in the brain and induction by cAMP. Haaning J, Oxvig C, Overgaard MT, Ebbesen P, Kristensen T, Sottrup-Jensen L. Eur J Biochem. 1996 Apr 1;237(1):159-63. PMID: 8620868
  4. Complex of pregnancy-associated plasma protein-A and the proform of eosinophil major basic protein. Disulfide structure and carbohydrate attachment. Overgaard MT, Sorensen ES, Stachowiak D, Boldt HB, Kristensen L, Sottrup-Jensen L, Oxvig C. J Biol Chem. 2003 Jan 24;278(4):2106-17. Epub 2002 Nov 5. PMID: 12421832


Search PubMed: Pregnancy-associated plasma protein-A


Prenatal Diagnosis Terms

  • false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.
  • false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.
  • negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.
  • positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
  • pre-implantation genetic diagnosis - (PGD) a screening procedure for embryos produced through in vitro fertilisation (IVF) for genetic diseases that would generate developmental abnormalities or serious postnatal diseases.
  • prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.
  • prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.

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Cite this page: Hill, M.A. (2014) Embryology Pregnancy-associated plasma protein-A. Retrieved April 25, 2014, from http://embryology.med.unsw.edu.au/embryology/index.php?title=Pregnancy-associated_plasma_protein-A

What Links Here?
Dr Mark Hill 2014, UNSW Embryology ISBN: 978 0 7334 2609 4 - UNSW CRICOS Provider Code No. 00098G
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