Pregnancy-associated plasma protein A and its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), are related to complexstenosis morphology in patients with stable angina pectoris.
[5] Nonstandard abbreviations: PAPP-A, pregnancy-associated plasma protein A; ACS, acute coronary syndrome; proMBP, proform of eosinophil major basic protein; FPAPP-A, free form of PAPP-A; TPAPP-A, total PAPP-A; cTnI, cardiac troponin I; ECG, electrocardiogram; CRP, C-reactive protein; FDA, US Food and Drug Administration; RR, risk ratio.
We analyzed the effect of increasing concentrations of PAPP-A/proMBP by the addition of purified PAPP-A/ proMBP (0 to 180 mg/L) to a reaction containing 1 nmol/L active PAPP-A.
QF-II was cleaved efficiently by recombinant PAPP-A, but not by an inactive mutated PAPP-A variant (E483Q) (25) or PAPP-A/ proMBP complex purified from pregnancy serum (21) (Fig.
The PAPP-A/proMBP assay imprecision was studied with pooled pregnancy serum diluted with BSA-TSA buffer to achieve PAPP-A/ proMBP concentrations relevant in ACS (mean PAPP-A/ proMBP concentrations, 3.1 mIU/L and 10.0 mN/L).
The calibration curves for the total PAPP-A and PAPP-A/ proMBP assays are shown in Fig.
In particular, PAPP-A in serum of patients with atherosclerotic disease appears to be present as a homodimer, making it difficult to measure PAPP-A as marker for coronary syndromes/ atherosclerosis by immunoassays that are designed to detect molecules in pregnancy serum via a sandwich formed by 2 antibodies, one specific for PAPP-A and the other specific for proMBP (10, 17).
[4] Nonstandard abbreviations: PAPP-A, pregnancy-associated plasma protein-A; IGF, insulin-like growth factor; proMBP, proform of eosinophil major basic protein; PAD, peripheral arterial disease; tHcy, total homocysteine; (hs-)CRP, (high-sensitivity) C-reactive protein; and eGFR, estimated glomerular filtration rate.
Recombinant full-length human
proMBP was produced with a plasmid also from Dr.
Because >99% of PAPP-A exists as the PAPP-A/
proMBP complex in the blood of pregnant women, polyclonal antisera raised against PAPP-A isolated from serum will invariably recognize the
proMBP part of the complex as well as the mature eosinophil MBP (2).
The synthesis of
ProMBP is known to occur in cells other than placental X cells and eosinophil precursor cells (18), but whether
ProMBP or MBP is released into the circulation from these sources is unknown.
Importantly,
proMBP antigen is present in excess of PAPP-A/proMBP complex, thus reflecting the presence of non-PAPP-A-containing
proMBP complexes--complexes that do not exist in a constant molar ratio to PAPP-A/proMBP complexes [241.