B-type Natriuretic Peptide circulating forms: Analytical and bioactivity issues

Specificity of B-Type Natriuretic Peptide Assays: Cross-Reactivity with Different BNP, NT-proBNP, and proBNP Peptides

“…In contrast, there was recognition of glycosylated proBNP molecules with the Bio-Rad and Goetze proBNP assays. The Bio-Rad proBNP assay recognizes the processing or "hinge" region of the molecule that is specific to proBNP indicating, and confirmed with our data, that there is no crossreactivity with BNP or NT-proBNP fragments (26 ). The Bio-Rad proBNP assay also additionally demonstrates cross-reactivity with glycosylated proBNP molecules, suggesting it may reflect the true amount of circulating nonglycosylated and glycosylated proBNP peptides.…”

Development of a BNP1-32 Immunoassay That Does Not Cross-React with proBNP

“…However, all current clinically approved BNP and NT-proBNP assays cross-react with proBNP, and all documented BNP assays also measure BNP metabolites to varying degrees (20,30 ). ProBNP has less than one-sixth of the biological activity of BNP1-32 (17 ) and metabolites of BNP also have lower activity, particularly when infused in vivo (15,16,31 ).…”

“…A future study to determine the amount of ring cleaved BNP1-32 detected by the BNP1-32 assay would require a step before the assay that reduces BNP to break the disulfide bond between the Cys10 and Cys26 of BNP. However, the concentration of such ring cleavage fragments is likely to be very low, owing to the low rates of hydrolysis of neprilysin on the BNP ring structure (30 ), and the absence of ring cleavage fragments from mass spectrometry studies (13,14 ).…”

The natriuretic peptides system in the pathophysiology of heart failure: from molecular basis to treatment

“…DPP IV also cleaves a similar histidine-proline dipeptide off the N-terminal end of proBNP, although at a 4-fold slower rate, to produce the truncated proBNP(3–108) form. This peptide circulates at relatively low concentrations in normal subjects, but proBNP(3–108) concentrations are raised in patients with asymptomatic LV dysfunction or HF (fiftieth percentiles 8, 18 and 43 pmol/l respectively) [56]. …”