Depletion of proBNP1-108 in patients with heart failure prevents cross-reactivity with natriuretic peptides.
BACKGROUND
After synthesis by cardiomyocytes, precursor proBNP1-108 is cleaved into NT-proBNP and BNP. Recently, cross-reactivity between these assays was discussed. The aim of this study was to characterize the cross-reactivities, through a new biochemical innovative approach consisting in the total depletion of the circulating proBNP1-108 in patients with heart failure (HF).


METHODS
This prospective study included 180 patients with chronic HF. BNP and NT-proBNP were dosed with commercial kits. ProBNP1-108 was determined using an ELISA research assay specific to the precursor. ProBNP1-108 depletion was performed by immunocapture with a specific antibody targeting exclusively the ProBNP1-108 hinge region. ProBNP1-108, BNP and NT-proBNP levels were determined before and after depletion using this process in HF patients.


RESULTS
Mean age was 74.34 +/-12.5 y, and 69% of patients were males. NYHA classes II and III were the most frequent (32% and 45% respectively). Before depletion, ProBNP1-108, NT-proBNP and BNP levels were 316.8+/-265.9 pg/ml; 6,054.0+/-11,539 pg/ml and 684.3+/-82.1 pg/ml respectively, and were closely correlated with NHYA classes. After immuno-depletion, proBNP1-108 was decreased in mean by 96% (p<0.0001), BNP by 53% (p<0.0001) and NT-proBNP by 5%. The relationship between BNP or NT-proBNP and NHYA classes remained unchanged.


CONCLUSIONS
Current BNP and NT-proBNP assays measured as well proBNP molecule. This cross reactivity percentage has been controversial. Thanks to the removal of circulating proBNP1-108 with our immunodepletion process, we are now able to assess the remaining "true" BNP and NT-proBNP molecules and further evaluate their clinical relevance.
Cardiology Department, University Hospital of Montpellier, Université de Montpellier 1, Montpellier, France ; Research Center, Montreal Heart Institute, Université de Montréal, Montreal, Quebec, Canada.
François
F
Roubille
Delphine
D
Delseny
Jean-Paul
JP
Cristol
Delphine
D
Merle
Nicolas
N
Salvetat
Catherine
C
Larue
Jean-Marc
JM
Davy
Florence
F
Leclercq
Jean-Luc
JL
Pasquie
Luc
L
Guerrier
Jeannette
J
Fareh
Anne-Marie
AM
Dupuy
D000368:Aged; D000369:Aged, 80 and over; D003429:Cross Reactions / Q000276:immunology; D005260:Female; D006333:Heart Failure / Q000175:diagnosis* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D020098:Natriuretic Peptide, C-Type / Q000276:immunology / Q000378:metabolism*; D045265:Natriuretic Peptides / Q000276:immunology / Q000378:metabolism*; D012307:Risk Factors
D045265:Natriuretic Peptides; C524086:Pro-BNP1-108; C480579:amino-terminal pro-C-type natriuretic peptide, human; D020097:Natriuretic Peptide, Brain; D020098:Natriuretic Peptide, C-Type