Acquired and congenital fast albumin bands; insights from electrospray TOF analysis of whole plasma into drug binding and albumin recycling

Abstract

ObjectivesTo define the underlying cause of unusual fast albumin bands detected on plasma protein electrophoresis of two patients. MethodPlasma was examined by electrospray time-of-flight mass spectrometry (TOF MS) to assess the possibility of congenital or acquired structural modifications. ResultsIn one patient whole protein MS indicated a drop of 486Da in the mass of 5.1% of the albumin molecules. This and the presence of an additional minor product (65,806Da) lacking a C-terminal phenylalanine (−147Da) indicated that this was albumin Rugby Park; an electrophoretically fast albumin variant caused by a splice site mutation (GT>CT) in intron 13 of the albumin gene. The second patient had an acquired alteration with a drift of albumin mobility to the anode. This severely ill patient was on intra venous antibiotics and electrospray TOF MS showed a stuttered repetition of the 66,439/66,558Da albumin isoforms at multiples of 455–459Da corresponding to the covalent attachment of 1, 2, 3 and 4 molecules of flucloxacillin. This modification of +455Da was also detected in a control on a 1g/day oral dose of flucloxacillin. ConclusionBoth aberrations were associated with diminished albumin concentrations. The C-terminal truncation of Rugby Park (albumin, 29g/l) likely interferes with receptor binding and albumin scavenging, while the 20g/l albumin in the second patient was mostly due to renal disease. In both cases electrospray TOF MS proved a rapid (5min) sensitive (0.2μl plasma) and highly informative way of analysing whole plasma or serum.