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.

Association of the IGF1/pregnancy-associated plasma protein-A system and adipocytokine levels with the presence and the morphology of carotid plaques in type 2 diabetes mellitus patients with stable glycaemic control

“…The absolute PAPP-A serum concentrations obtained in our study sample may, therefore, not be directly comparable with the PAPP-A concentrations reported by other authors (10,15,18,31,32) because of the different methods used for PAPP-A measurement. It is well known that atherosclerosis-related PAPP-A differs from pregnancy-related PAPP-A, since the first circulates as a homodimeric active form, uncomplexed with the proform of the eosinophil major basic protein (proMBP).…”

“…It is well known that atherosclerosis-related PAPP-A differs from pregnancy-related PAPP-A, since the first circulates as a homodimeric active form, uncomplexed with the proform of the eosinophil major basic protein (proMBP). Immunoassays used to detect total PAPP-A may not be accurate (32). Thus, we used an ultrasensitive PAPP-A ELISA developed for measuring PAPP-A molecules but not the proMBP subunit to avoid false positive results.…”

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

“…We tested the performance of the DRG ELISA with 4 ACS serum samples (from 4 AMI patients) that contained high concentrations of PAPP-A (19.2 mIU/L, 22.8 mIU/L, 49.4 mIU/L, and 145.0 mIU/L, respectively) measured with our total PAPP-A assay, and we found that only the sample that had a PAPP-A concentration of 145.0 mIU/L was actually measurable with the DRG ELISA. Thus, the negative study results obtained by Dominguez-Rodriguez et al are quite understandable and highlight the importance of the selection of proper immunoassays for PAPP-A measurement in the ACS samples, as we previously pointed out (23 ).…”

Randomised Assessment of Treatment using Panel Assay of Cardiac markers – Contemporary Biomarker Evaluation (RATPAC CBE)

“…[215][216][217] Different assays may therefore perform differently. 218 It has been shown that free PAPP-A is a better predictor than total PAPP-A.…”