Pregnancy associated plasma protein-A: ultrasensitive immunoassay and determination in coronary heart disease.
OBJECTIVE
Markers of myocardial injury have been vital in the assessment of patients with coronary heart disease. Pregnancy associated plasma protein A (PAPP)-A is an insulin-like growth factor (IGF) binding protein (IGFBP)-4 protease and a potential early indicator of unstable angina. We developed an ultrasensitive enzyme-linked immunosorbent assay (ELISA) for PAPP-A and measured serum PAPP-A in patients with biochemical evidence of acute coronary syndrome.


METHODS
Method development was based on pair-wise evaluation of a panel of antibodies and determination of PAPP-A specificity and sensitivity relative to those of a conventional method. Association of PAPP-A with myocardial damage was assessed in serum samples classified based on serum creatine kinase (CK)-MB or cardiac troponin-T levels.


RESULTS
Serum PAPP-A was significantly higher in samples with elevated CK-MB or troponin-T than in samples with normal CK-MB (p < 0.001). Marker-association studies showed strong correlation between PAPP-A and troponin-T (r = 0.59, p < 0.001) in a subset of troponin-T positive samples. Indications for both parallel as well as divergence in the expression of PAPP-A and troponin-T was also evident when serial timed samples available from a number of patients were analyzed.


CONCLUSIONS
The data are consistent with the conclusion that expression of PAPP-A is enhanced in patients with biochemical evidence of acute coronary syndrome and suggest strongly that demonstration of PAPP-A association with other cardiac markers might be influenced by their relative release dynamics (timing and duration). The availability of the ultrasensitive PAPP-A ELISA should facilitate systematic investigations of PAPP-A expression in this and other pathophysiological conditions that might involve altered expression of the IGF/PAPP-A system.
Khosravi
Javad
J
Diagnostic Systems Laboratories (Canada) Inc., Toronto, Ontario, Canada. jkhosravi@mtsinai.on.ca
Diamandi
Anastasia
A
Krishna
Radha G
RG
Bodani
Umesh
U
Mistry
Jehangir
J
Khaja
Najmuddin
N
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis; D003402:Creatine Kinase / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000276:immunology / Q000378:metabolism*; D012044:Regression Analysis; D012680:Sensitivity and Specificity; D020107:Troponin T / Q000097:blood
D000906:Antibodies; D015415:Biomarkers; D020107:Troponin T; D003402:Creatine Kinase; D011266:Pregnancy-Associated Plasma Protein-A