An Immunoluminometric Assay for N-terminal Pro-Brain Natriuretic Peptide: Development of a Test for Left Ventricular Dysfunction

Clin Sci (Lond). 1999 Apr;96(4):373-80.

Abstract

Measurement of plasma levels of brain natriuretic peptide (BNP) has been used to assess left ventricular dysfunction and prognosis. Levels of the N-terminus of the precursor of BNP (NT-proBNP) have been reported to be elevated to a greater extent than BNP in left ventricular dysfunction. We have devised a non-radioactive sensitive and specific assay for NT-proBNP based on a competitive ligand binding principle. The chemiluminescent label 4-(2-succinimidyloxycarbonylethyl)phenyl-10-methylacridinium 9-carboxylate fluorosulphonate was used to label peptides representing domains in the middle and C-terminal sections of NT-proBNP. Assay of the C-terminal section of NT-proBNP (amino acids 65-76) in patients with proven left ventricular dysfunction [left ventricular wall motion index median 0.9 (range 0.3-1.4)] revealed elevated values [median 639 (386-911) fmol/ml] compared with normal controls [left ventricular wall motion index of 2 in all, NT-proBNP median 159 (120-245) fmol/ml, P<0.001]. Measurement of the middle section of NT-proBNP (amino acids 37-49) was not a discriminating test. It is thus possible to derivatize small peptides with a methyl acridinium label and preserve immunodetection with specific antibodies. Such methodology may allow non-radioactive immunoluminometric assays to be devised.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Case-Control Studies
  • Echocardiography
  • Female
  • Humans
  • Immunoassay
  • Luminescent Measurements
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain
  • Nerve Tissue Proteins / blood*
  • Peptide Fragments / blood*
  • Ventricular Dysfunction, Left / blood
  • Ventricular Dysfunction, Left / diagnosis*

Substances

  • Biomarkers
  • Nerve Tissue Proteins
  • Peptide Fragments
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain