Immunoassays developed for pregnancy-associated plasma protein-A (PAPP-A) in pregnancy may not recognize PAPP-A in acute coronary syndromes.

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.