Modified Form of the Fibrinogen Bβ Chain (des-Gln Bβ), a Potential Long-Lived Marker of Pancreatitis

Abstract

AbstractBackground: During an investigation of genetic variants of fibrinogen, we observed a novel form of the Bβ chain, with a mass decrease of approximately 128 Da, in one of the controls. The plasma sample originated from an individual who had experienced acute pancreatitis a week earlier but whose serum amylase activity had returned to normal. We investigated the structure of the modified fibrinogen and explored its relationship to pancreatic disease.Method: Fibrinogen was isolated from the plasma of 9 individuals with increased pancreatic amylase activity (114–1826 U/L) and presumed pancreatitis and from 6 control individuals with amylase activities <56 U/L. Fibrinogen (or fibrin) Bβ chains were isolated by reversed-phase HPLC and analyzed directly by electrospray ionization mass spectrometry. Tryptic and CNBr peptide mapping and thrombin treatment pinpointed the location of the 128-Da loss in mass.Results: The acquired fibrinogen Bβ chain modification was attributable to the loss of its C-terminal glutamine residue. Incubating purified fibrinogen with pancreatic carboxypeptidase A (CpA) produced an identical modification. The des-Gln Bβ fibrinogen accounted for >80% of the Bβ chains in 3 of the individuals with increased amylase but only approximately 5% of the Bβ chains in control samples.Conclusion: Pancreatic CpA activity is used as an index of acute pancreatic disease, but given that the circulatory half-lives of fibrinogen and CpA are approximately 4 days and only 2.5 h, respectively, measuring des-Gln Bβ fibrinogen, the in vivo product of CpA activity, could provide clinicians with retrospective evidence of disease.