Pregnancy-associated plasma protein-A (PAPP-A) was first identified as a high-molecular weight constituent in human pregnancy serum. In the blood of pregnant women PAPP-A exists as a covalent (disulfide bridged) heterotetrameric complex, consisting of two 200 kDa PAPP-A subunits and two 50-90 kDa subunits of the proform of eosinophil major basic protein (proMBP). Such complex is denoted as heterotetrameric PAPP-A (PAPP-A/proMBP or htPAPP-A). It was shown that proMBP has inhibitory properties against protease activity of PAPP-A in htPAPP-A heteromeric complex.
htPAPP-A is widely recognized biochemical marker of Down syndrome (DS) used in the first trimester of pregnancy. htPAPP-A level in maternal serum increases with gestational age until term. In case of DS pregnancy, htPAPP-A concentration in the first trimester is markedly decreased. So, currently htPAPP-A is used as a biochemical marker of DS in the first trimester of pregnancy in combination with free β-subunit of chorionic gonadotropin (βhCG) and nuchal translucency. Before this combination of markers was established, biochemical screening for DS was performed only in the second trimester (16-18 gestational weeks). Thus new approach in the DS screening allows starting medical intervention significantly earlier comparing with the previously used methods.
Recently it was shown that another form of protein – homodimeric PAPP-A (dPAPP-A) with molecular mass about 400 kDa, is abundantly expressed in unstable coronary atherosclerotic plaques. It has also been demonstrated that blood level of dPAPP-A is significantly elevated in patients with unstable angina or acute myocardial infarction in comparison with patients with stable angina and control subjects. In addition, dPAPP-A has also been shown to be a strong independent marker of risk stratification for patients with acute coronary syndrome (ACS). The ACS-related form of PAPP-A, presumably originating from ruptured plaque, is not complexed with proMBP subunit, like it is htPAPP-A. Therefore it is supposed, that in atherosclerotic plaque dPAPP-A functions as is an active protease and can promote IGF release. Thus, it may be speculated that dPAPP-A influences to the transformation of a stable atherosclerotic plaque into an unstable one. Such involvement of dPAPP-A in the pathophysiology of ACS suggests that it may serve as a marker of plaque destabilization and PAPP-A measurements in patient’s blood could be very helpful in identifying patients at the very beginning of the process of plaque disruption.
Structural difference of dPAPP-A from pregnancy related htPAPP-A makes possible immunochemical discriminations of these two PAPP-A forms. Antibodies, specific to dPAPP-A and having no cross-reaction with htPAPP-A, could be used for the development of immunoassays for precise selective dPAPP-A measurements in human blood.
Advanced ImmunoChemical represents the biggest world supplier of htPAPP-A antigen purified from retroplacental blood. Now Advanced ImmunoChemical offers a new product – recombinant dPAPP-A. We also offer PAPP-A and proMBP specific monoclonal antibodies suitable for the development of highly sensitive and rapid sandwich-type PAPP-A immunoassays for quantitative detection of htPAPP-A in maternal blood as well as for detection of dPAPP-A in the blood of ACS patients. We also present here new generation of dPAPP-A specific monoclonal antibodies recognizing only recombinant and atherosclerotic dPAPP-A and having no cross-reaction with htPAPP-A form of antigen.
References:
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