Immunoassays Developed for Pregnancy-Associated Plasma Protein-A (PAPP-A) in Pregnancy May Not Recognize PAPP-A in Acute Coronary Syndromes

Abstract Background: Pregnancy-associated plasma protein-A (PAPP-A) concentrations are increased in the circulation of patients with acute coronary syndromes (ACS) and are associated with future adverse cardiac events. PAPP-A in ACS differs from PAPP-A in pregnancy in that PAPP-A in ACS is not complexed with the proform of eosinophil major basic protein (proMBP). We investigated the effect of antibody selection on the utility of PAPP-A assays for measurement of PAPP-A in pregnancy and/or ACS, and whether immunoassays for PAPP-A in pregnancy are suitable for PAPP-A in ACS. Methods: We constructed 2-site sandwich time-resolved immunofluorometric assays using 22 monoclonal antibodies raised against pregnancy serum PAPP-A. All antibodies were studied in pairs, with each antibody used as either capture or tracer. We compared the reactivity of each antibody combination with PAPP-A/proMBP complex derived from pregnancy sera or with uncomplexed PAPP-A extracted from atherosclerotic plaques. Recombinant human PAPP-A and proMBP were also used to determine the specificity of the antibodies. We confirmed all major findings with serum samples collected from patients with myocardial infarction. Results: Six monoclonal antibodies reacted with the proMBP subunit of the PAPP-A/proMBP complex. Epitopes of 3 proMBP-reactive antibodies largely overlapped, but were well separated from those of another group of 3 proMBP-reactive antibodies. Assays using any of the 6 proMBP-reactive antibodies failed to detect PAPP-A in ACS. In addition, some 2-site assays capable of detecting PAPP-A in pregnancy were almost incapable of detecting PAPP-A in ACS, although the individual epitopes remained detectable in PAPP-A in ACS. Conclusions: Immunoassays developed for PAPP-A in pregnancy may not be suitable for PAPP-A in ACS. Assays for PAPP-A in ACS should be based on careful antibody selection and subjected to extensive testing with clinical ACS samples.

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Comment on Immunoassays Developed for Pregnancy-Associated Plasma Protein-A (PAPP-A) in Pregnancy May Not Recognize PAPP-A in Acute Coronary Syndromes

Clinical Chemistry ◽

10.1373/clinchem.2006.074138 ◽

2006 ◽

Vol 52 (8) ◽

pp. 1619-1620 ◽

Cited By ~ 6

Author(s):

Salim Fredericks ◽

Vicente Bertomeu-Gonzalez ◽

Ivana Petrovic ◽

David W Holt ◽

Juan Carlos Kaski

Keyword(s):

Plasma Protein ◽

Acute Coronary Syndromes ◽

Protein A ◽

Coronary Syndromes ◽

In Pregnancy

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Sex differences in pregnancy associated plasma protein-A (PAPP-A) concentrations in patients with acute coronary syndromes

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2008.08.025 ◽

2008 ◽

Vol 41 (14-15) ◽

pp. 1271-1272

Author(s):

P. Kavsak ◽

A.R. MacRae ◽

M.J. Yerna ◽

A.S. Jaffe

Keyword(s):

Sex Differences ◽

Plasma Protein ◽

Acute Coronary Syndromes ◽

Protein A ◽

Coronary Syndromes ◽

In Pregnancy

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Intravenous Administration of Low Molecular Weight and Unfractionated Heparin Elicits a Rapid Increase in Serum Pregnancy-Associated Plasma Protein A

Clinical Chemistry ◽

10.1373/clinchem.2008.108738 ◽

2009 ◽

Vol 55 (6) ◽

pp. 1214-1217 ◽

Cited By ~ 30

Author(s):

Risto Tertti ◽

Saara Wittfooth ◽

Pekka Porela ◽

K E Airaksinen ◽

Kaj Metsärinne ◽

...

Keyword(s):

Molecular Weight ◽

Coronary Angiography ◽

Unfractionated Heparin ◽

Plasma Protein ◽

Intravenous Administration ◽

Acute Coronary Syndromes ◽

Protein A ◽

Low Molecular Weight ◽

Dialysis Session ◽

Coronary Syndromes

Abstract Background: Pregnancy-associated plasma protein A (PAPP-A) has been suggested as a useful diagnostic and prognostic marker in acute coronary syndromes. Because low molecular weight heparin (LMWH) and unfractionated heparin (UFH) are commonly used in these cases, we analyzed the effects of intravenous administration of these heparins on serum PAPP-A concentrations. Methods: Serum concentrations of total and free PAPP-A were analyzed in 14 patients on chronic hemodialysis and in 10 coronary angiography patients. Ten of the dialysis patients received standard LMWH anticoagulation at the start of dialysis, and 4 were treated with a heparin-free method. Two of the patients on heparin-free hemodialysis received a reduced LMWH bolus 2 h after the start of dialysis. All angiography patients received UFH at the start of the procedure, and 1 patient received 2 extra boluses of UFH. Serum PAPP-A concentrations were analyzed before and during the dialysis session and during the coronary angiography examination. Results: A rapid increase in total PAPP-A (median, 25-fold) was seen in all patients within 5 min of administration for both LMWH and UFH boluses. This response was due to an increase in free PAPP-A in the serum. PAPP-A did not increase significantly in the patients who underwent heparin-free hemodialysis. Repeated heparin boluses induced a new PAPP-A release. In vitro addition of heparins to samples of whole blood did not increase PAPP-A concentrations. Conclusions: Intravenous administration of heparin induces an intense and rapid increase in free PAPP-A in the serum. We recommend that this effect be considered when PAPP-A is assessed as a biomarker in acute coronary syndromes.

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