MS-based phenotypic characterization of a human blood protein from urinary waste products

The urine proteome (urineome) has become an ideal biological fluid for biomarker study and detection due to its rich protein content as well as its ease and abundance in collection. Protein variation in human plasma has been linked to the presence of disease states in humans; however, it stands to reason that the same is true of the equally complex urineome. In this manuscript we present the combination of two proteomics technologies, mass spectrometric immunoassay and a bioreactive probe, for the detection and characterization of the protein variants of transthyretin (TTR) found in human urine. Coupling these two technologies we could precisely identify protein variants within a population of normal individuals. This is the first report of the detailed characterization of urinary TTR using this combination of proteomic analytical techniques, and demonstrates a novel non-invasive methodology for the routine analysis of this clinically significant urine protein target.