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Blood, 1 March 2007, Vol. 109, No. 5, pp. 1971-1974. Prepublished online as a Blood First Edition Paper on November 2, 2006; DOI 10.1182/blood-2006-08-040956. This Article Full Text (PDF) All Versions of this Article: blood-2006-08-040956v1 109/5/1971    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tennent, G. A Articles by Pepys, M. B Search for Related Content PubMed PubMed Citation Articles by Tennent, G. A Articles by Pepys, M. B Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 11, 2006 Accepted October 13, 2006 Human plasma fibrinogen is synthesized in the liver Glenys A Tennent*, Stephen O Brennan, Arie J Stangou, John O'Grady, Philip N Hawkins, and Mark B Pepys Royal Free and University College Medical School, United Kingdom Christchurch Hospital, New Zealand King's College Hospital, United Kingdom * Corresponding author; email: g.tennent{at}medsch.ucl.ac.uk. Hereditary systemic amyloidosis caused by fibrinogen A-chain gene mutations is an autosomal dominant condition with variable penetrance, usually of late onset, and typically presents with nephropathy leading to renal failure. Amyloid deposits often develop rapidly in transplanted kidneys, and concomitant orthotopic liver transplantation has lately been performed in several patients with the hope of halting amyloid deposition. Fibrinogen is produced in vitro by hepatocytes, but also by other human cell types and although the liver is the source of plasma fibrinogen in vivo in rats this is not known in humans. Transplantation of livers expressing wild-type fibrinogen into patients with variant fibrinogen amyloidosis provides a unique opportunity to establish the source of human plasma fibrinogen. We therefore characterized plasma fibrinogen A-chain allotypes by electrospray ionization mass spectrometry mapping of tryptic digests before and after liver transplantation. Before liver transplantation, fibrinogen amyloidosis patients with the Glu526Val A-chain variant had approximately equal proportions of peptide with the wild-type sequence, TFPGFFSPMLGEFVSETESR, and with the amyloidogenic variant sequence TFPGFFSPMLGEFVSVTESR, as expected for individuals heterozygous for the mutation. After transplantation only the wild-type sequence was detected, and the liver is thus the source of at least 98% of the circulating fibrinogen. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Polterauer, C. Grimm, V. Seebacher, N. Concin, C. Marth, C. Tomovski, H. Husslein, H. Leipold, K. Hefler-Frischmuth, C. Tempfer, et al. Plasma Fibrinogen Levels and Prognosis in Patients with Ovarian Cancer: A Multicenter Study Oncologist, October 1, 2009; 14(10): 979 - 985. [Abstract] [Full Text] [PDF] J. D. Gillmore, H. J. Lachmann, D. Rowczenio, J. A. Gilbertson, C.-H. Zeng, Z.-H. Liu, L.-S. Li, A. Wechalekar, and P. N. Hawkins Diagnosis, Pathogenesis, Treatment, and Prognosis of Hereditary Fibrinogen A{alpha}-Chain Amyloidosis J. Am. Soc. Nephrol., February 1, 2009; 20(2): 444 - 451. [Abstract] [Full Text] [PDF]

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