Received on March 23, 2006
Accepted on June 5, 2006

Point-of-Care Testing

Immunofluorometric Point-of-Care Assays for the Detection of Acute Coronary Syndrome Related Noncomplexed Pregnancy-Associated Plasma Protein A

¹ Department of Biotechnology, University of Turku, Turku, Finland
² Department of Medicine, University of Turku, Turku, Finland
³ Department of Medicine, University of Helsinki, Helsinki, Finland
⁴ Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland
⁵ Innotrac Diagnostics Oy, Turku, Finland

^* To whom correspondence should be addressed. E-mail: saara.wittfooth{at}utu.fi.

Background: We recently reported that the pregnancy-associated plasma protein A (PAPP-A) form, specifically related to acute coronary syndromes (ACS), is not complexed with the proform of eosinophil major basic protein (proMBP). The aim of this study was to develop rapid point-of-care immunoassays for the measurement of the noncomplexed PAPP-A.

Methods: We developed immunofluorometric noncompetitive dry-reagent assays for total PAPP-A with 2 PAPP-A, subunit-specific, monoclonal antibodies and for PAPP-A/proMBP complex with 1 PAPP-A subunit-specific antibody and 1 proMBP subunit-specific antibody. The concentration of noncomplexed PAPP-A was determined as the difference of the results obtained with the 2 assays.

Results: The assays were linear from 0.5 to 300 mIU/L. The analytical detection limit and functional detection limit (CV <20%) were 0.18 mIU/L and 0.27 mIU/L for total PAPP-A assay and 0.23 mIU/L and 0.70 mIU/L for PAPP-A/proMBP assay, respectively. The total assay imprecisions were <10%, and recoveries were 88%-107% for both assays. The mean difference (95% limits of agreement) between the new total PAPP-A assay and a previously reported total PAPP-A assay was -3.2% (-45.7% to 39.3%; n = 546; P = 0.0019). In serum samples from 159 non-ACS individuals, median concentrations (interquartile range) were 2.42 (1.14) mIU/L for total PAPP-A, 2.20 (1.18) mIU/L for PAPP-A/proMBP, and 0.18 (0.63) mIU/L for noncomplexed PAPP-A. Total PAPP-A and PAPP-A/proMBP, but not noncomplexed PAPP-A, correlated with age (r = 0.290, P = 0.0002; r = 0.230, P = 0.0035; r = 0.075, P = 0.3483, respectively).

Conclusions: The new assays described revealed that noncomplexed PAPP-A is found only in negligible amounts in non-ACS samples. Studies are now needed to demonstrate its clinical usefulness in ACS patients.