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Background  After synthesis by cardiomyocytes, precursor proBNP 1-108  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 proBNP 1-108  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. ProBNP 1-108  was determined using an ELISA research assay specific to the precursor. ProBNP 1-108  depletion was performed by immunocapture with a specific antibody targeting exclusively the ProBNP 1-108  hinge region. ProBNP 1-108 , 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, ProBNP 1-108 , 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, proBNP 1-108  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.    Conclusion  Current BNP and NT-proBNP assays measured as well proBNP molecule. This cross reactivity percentage has been controversial. Thanks to the removal of circulating proBNP 1-108  with our immunodepletion process, we are now able to assess the remaining “true” BNP and NT-proBNP molecules and further evaluate their clinical relevance.

Depletion of proBNP1-108 in Patients with Heart Failure Prevents Cross-Reactivity with Natriuretic Peptides