Maternal serum concentrations of pregnancy-associated plasma protein A (PAPP-A, EC 3.4.24.79, papalysin-1) are used to predict occurrence of Down syndrome. During pregnancy, PAPP-A is produced in high concentrations by the trophoblast and released into maternal circulation. In pregnancy, PAPP-A primarily circulates as 500-kDa heterotetrameric 2:2 complex with the proform of eosinophil major basic protein (proMBP), which inhibits the proteolytic activity of PAPP-A. Dimeric PAPP-A is the only active form and proteolyses IGFBP-4 and IGFBP-5. Significant amounts of active PAPP-A is reported at gestational ages between seven and thirteen weeks.

References:
1. HHS Publication, 5th ed., 2007. Biosafety in Microbiological and Biomedical Laboratories. Available http://www.cdc.gov/biosafety/publications/bmbl5/BMBL5
2. Approved Guideline – Procedures for the Handling and Processing of Blood Specimens, H18-A3. 2004. Clinical and Laboratory Standards Institute.
3. Kricka L. Interferences in immunoassays – still a threat. Clin Chem 2000; 46: 1037–1038.

PAPP-A CLIA AL-206
Kumar A, Kalra B, Patel A, Oxvig C. Development of a well characterized Total PAPP-A chemiluminescent assay for maternal serum evaluation. Poster session presented at the 94th Annual Endocrine Society Meeting; 2012 Jun 23-26; Houston, TX.

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PAPP-A ELISA AL-106
Babiker A, Al Noaim K, Al Swaid A, et al. Short stature with low insulin-like growth factor 1 availability due to pregnancy-associated plasma protein A2 deficiency in a Saudi family. Clin Genet. 2021;100(5):601-606. doi: 10.1111/cge.14030.

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Buhimschi IA, Zhao G, El Helou Y, Frye LJ, Winikoff B, Raymond EG. . Analytical Comparison of Pregnancy-Associated Plasma Protein-A (PAPP-A) Immunoassays for Biochemical Determination of Gestational Age. J Appl Lab Med. 2021 Jul 30;jfab057. doi: 10.1093/jalm/jfab057

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Donegan D, Bale LK, Conover CA. PAPP-A in normal human mesangial cells: effect of inflammation and factors related to diabetic nephropathy. J Endocrinol. 2016 Oct;231(1):71-80. doi: 10.1530/JOE-16-0205. Epub 2016 Aug 12. PMID: 27519211.

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Espelund U, Renehan AG, Cold S, Oxvig C, Lancashire L, Su Z, Flyvbjerg A, Frystyk J. Prognostic relevance and performance characteristics of serum IGFBP-2 and PAPP-A in women with breast cancer: a long-term Danish cohort study. Cancer Med. 2018;7(6):2391-2404. doi:10.1002/cam4.1504.

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Espelund US, Bjerre M, Hjortebjerg R, Rasmussen TR, Lundby A, Hoeflich A, Folkersen BH, Oxvig C, Frystyk J. Insulin-Like Growth Factor Bioactivity, Stanniocalcin-2, Pregnancy-Associated Plasma Protein-A, and IGF-Binding Protein-4 in Pleural Fluid and Serum From Patients With Pulmonary Disease. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3526-3534.

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Frye LJ, Buhimschi IA, Raymond EG, Zhao G, Winikoff B. PAPP-A as a screening tool for assessment of gestational age before medication abortion in an intended-use population. Biomark Med. 2023;17(2):73-85. doi:10.2217/bmm-2022-0653.

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Gude MF, Hjortebjerg R, Oxvig C, Thyø AA, Magnusson NE, Bjerre M, Pedersen SB, Frystyk J. PAPP-A, IGFBP-4 and IGF-II are secreted by human adipose tissue cultures in a depot-specific manner. Eur J Endocrinol. 2016 Dec;175(6):509-519. doi: 10.1530/EJE-16-0569. Epub 2016 Sep 1. PMID: 27585595.

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Hjortebjerg R, Pedersen DA, Mengel-From J, Jørgensen LH, Christensen K, Frystyk J. Heritability and circulating concentrations of pregnancy-associated plasma protein-A and stanniocalcin-2 in elderly monozygotic and dizygotic twins. Front Endocrinol (Lausanne). 2023;14:1193742. doi:10.3389/fendo.2023.1193742.

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Hjortebjerg R, Rasmussen LM, Gude MF, Irmukhamedov A, Riber LP, Frystyk J, De Mey JGR. Local IGF Bioactivity Associates with High PAPP-A Activity in the Pericardial Cavity of Cardiovascular Disease Patients. J Clin Endocrinol Metab. 2020 Nov 1;105(11):dgaa617. doi: 10.1210/clinem/dgaa617. PMID: 32875328.

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Hjortebjerg R, Thomsen KL, Agnholt J, Frystyk J. The IGF system in patients with inflammatory bowel disease treated with prednisolone or infliximab: potential role of the stanniocalcin-2 / PAPP-A / IGFBP-4 axis. BMC Gastroenterol. 2019 Jun 3;19(1):83. doi: 10.1186/s12876-019-1000-6. PMID: 31159802; PMCID: PMC6547608.

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Keikkala E, Forstén J, Ritvos O, Stenman UH, Kajantie E, Hämäläinen E, Räikkönen K, Villa PM, Laivuori H. Serum Inhibin-A and PAPP-A2 in the prediction of pre-eclampsia during the first and second trimesters in high-risk women. Pregnancy Hypertens: . 2021 Aug;25:116-122.doi: 10.1016/j.preghy.2021.05.024. Epub 2021 Jun 2.

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Lambert-Messerlian GM, Eklund EE, Neveux LM, Palomaki GE. Measuring maternal serum screening markers for Down’s syndrome in plasma collected for cell-free DNA testing. J Med Screen. 2017 Sep;24(3):113-119.

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Martín-Rivada Á, Guerra Cantera S, Campillo-Calatayud A, Andrés-Esteban EM, Sánchez Holgado M, Martos-Moreno GÁ, Pozo J, Güemes M, Soriano-Guillén L, Pellicer A, Oxvig C, Frystyk J, Chowen JA, Barrios V, Argente J. Pappalysins and Stanniocalcin and Their Relationship With the Peripheral IGF Axis in Newborns and During Development. J Clin Endocrinol Metab. 2022 Sep 28;107(10):2912-2924. doi: 10.1210/clinem/dgac453. PMID: 35902207.

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Salameh M, Lee J, Palomaki G, Eklund E, Curran P, Suarez JAR, Lambert-Messerlian G, Bourjeily G. . Snoring and markers of fetal and placental wellbeing. Clin Chim Acta. 2018 Oct;485:139-143. doi: 10.1016/j.cca.2018.06.039

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