Pregnancy-associated plasma protein A (PAPP-A) Antibodies

Pregnancy-associated Plasma Protein A (PAPP-A)

Pregnancy-associated plasma protein A (PAPP-A) is a 200 kDa metalloproteinase specific for insulin-like growth factor 4 (IGF-4) that forms a homodomer of 400 kDa in active form.  In the serum of pregnant women it exists as a heterotetramer with pro-eosinophil basic protein (proEBP; 2:2 ratio of PAPP-A to proEBP) with the proEBP maintaining the metalloproteinase in an inactive form^1-2.  More recently, PAPP-A has been shown to be a promising marker for unstable atherosclerotic plaques with potential as a prognostic indicator for elevated risk in patients with cardiovascular disease^3-5. With the recent development of highly specific antibodies for the dimeric form of PAPP-A, it has been demonstrated that it is the dimeric form of PAPP-A that becomes elevated in the serum of patients with cardiovascular disease, not the form complexed with proEBP^6,7.

AvantGenhas developed compatible high affinity human monoclonal diagnostic antibodies that specifically identify the PAPP-A subunit relevant to cardiovascular disease for diagnostic purposes and show no cross-reactivity to either proEBP or related metalloproteinases such as PAPP-A2 or MMP-9.

References:
1. Lawrence, JB.,et al., The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc. Natl. Acad. Sci U. S. A. 1999; 96, 3149–3153.

2. Oxvig, C., et al., Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein. J. Biol. Chem. 1993; 268,12243–12246.

3. Bayes-Genis A., et al., Pregnancy-associated plasma protein A as a marker of acute coronary syndromes. N Engl J Med. 2001; 345(14):1022-9.

4. Iversen, KK., et al., CLARICOR Trial Group.Pregnancy associated plasma protein-A as a marker for myocardial  infarction and death in patients with stable coronary artery disease: a prognostic study within the CLARICOR Trial. Atherosclerosis. 2011;214(1):203-8.

5. Qin QP.,et al., Molecular distinction of circulating pregnancy-associated plasma protein A in myocardial infarction and pregnancy. Clin Chem. 2005; 51(1):75-83.

6. Kavsak, PA, et al., PAPP-A as a marker of increased long-term risk in patients with chest pain. ClinBiochem. 2009; 42(10-11):1012-8.

7. Lund, J., et al., Free vs total pregnancy-associated plasma protein A (PAPP-A) as a predictor of 1-year outcome in patients presenting with non-ST-elevation acute coronary syndrome. Clin Chem. 2010; 56(7):1158-65.