Key result
Mass spectrometry analysis of plasma from heart failure patients and healthy controls detected 16 previously unknown circulating fragments of proBNP peptides.
Why the study?
Variably O-glycosylated and degraded proBNP-derived molecular forms challenge immunoassays due to cross-reactivity differences, requiring better molecular characterization.
Observational (n=10)
The identification of 16 previously unknown circulating proBNP fragments highlights the high molecular complexity and degradation of these biomarkers, which may inform the design of more accurate future immunoassays.
May improve proBNP assay design; leaves open clinical validation of fragment-specific measurements.
BACKGROUND: The high molecular complexity of variably O-glycosylated and degraded pro B-type natriuretic peptide (proBNP) derived molecular forms challenges current immunoassays. Antibodies used show pronounced differences in cross-reactivities with these circulating fragments, which still need to be better characterized on a molecular level. To pave the way for advanced quantitative assays in the future, it is critical to fully understand these circulating forms. METHODS: Plasma samples were collected from 8 heart failure (HF) patients and 2 healthy controls. NT-proBNP and proBNP were purified by immunoprecipitation and analyzed by nano-flow liquid chromatography coupled to high-resolution mass spectrometry. Fragments formed during proteolysis in solution digestion were distinguished from naturally occurring peptides by using an 18O stable isotope labeling strategy. RESULTS: We detected 16 previously unknown circulating fragments of proBNP peptides (9 of which are located in the N-terminal and 7 in the C-terminal region), revealing a more advanced state of degradation than previously known. Two of these fragments are indicative of either unidentified processing modes or a far-reaching C-terminal degradation (or a combination thereof) of the precursor proBNP. CONCLUSIONS: Our results further restrict ideal target epitopes for immunoassay antibodies and expand the current thinking of diversity, degradation, and processing of proBNP, as well as the distribution of circulating forms.
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Amplatz et al. (2020) conducted an observational in Heart failure (n=10). Heart failure vs. Healthy controls was evaluated on Detection of circulating fragments of proBNP peptides. Mass spectrometry analysis of plasma from heart failure patients and healthy controls detected 16 previously unknown circulating fragments of proBNP peptides.
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