PAPP-A Technotes

Pregnancy-associated plasma protein-A (PAPP-A) is a metalloprotease that belongs to the metzincin superfamily of zinc peptidases. Its main substrate is insulin-like growth factor binding protein (IGFPB) 4. This cleavage causes release of bound IGF, which plays an important role in promoting cell differentiation and proliferation. PAPP-A was first identified from the serum of pregnant women, hence its name. Later, it was shown to be expressed in multiple tissues.

Two forms of PAPP-A

Heterotetrameric PAPP-A (htPAPP-A) is a screening marker for Down syndrome. htPAPP-A level in maternal serum increases with gestational age until term. If the concentration of htPAPP-A in the first trimester is markedly decreased, this indicates a higher risk of Down syndrome (1).

htPAPP-A is a protein complex consisting of two PAPP-A subunits and two proforms of eosinophil basic proteins (proMBP) covalently linked to each other. proMBP has been shown to inhibit the protease activity of PAPP-A in this heteromeric complex (2).

Homodimeric PAPP-A (dPAPP-A) is abundantly expressed in unstable coronary atherosclerotic plaques (3). dPAPP-A circulates as a homodimer and not in complex with proMBP. Based on several studies dPAPP-A has been considered to be a promising marker of plaque destabilization in patients with acute coronary syndrome (ACS). Unfortunately, dPAPP-A assays have been shown to also detect htPAPP-A, the Down syndrome marker not related to atherosclerotic plaques. In order to prevent this, a dPAPP-A assay should be designed so that it only recognizes dPAPP-A and does not cross-react with htPAPP-A.

Another limitation to the use of dPAPP-A as a cardiac marker is the fact that the measurements were shown to be affected by heparin, an anti-coagulation agent often used as part of the treatment procedure with patients suffering from acute myocardial infarction. So in order to use dPAPP-A as a cardiac biomarker the heparin injections should be taken into account when analyzing the samples.

Reagents for immunoassay development

We provide monoclonal antibodies (MAbs) specific to PAPP-A and proMBP that allow for the development of highly sensitive, quantitative htPAPP-A immunoassays. We also provide reagents for the development of dPAPP-A specific assay. In addition, we provide htPAPP-A antigen purified from retroplacental blood. Hytest is the largest global supplier of this product.