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Semin Thromb Hemost 2006; 32(2): 155-159
DOI: 10.1055/s-2006-939771
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Membrane Cofactor Protein and Factor I: Mutations and Transplantation

David Kavanagh1 , Timothy H.J. Goodship1
  • 1Institute of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom
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Publication History

Publication Date:
30 March 2006 (online)

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ABSTRACT

Mutations in the genes for three complement regulators-complement factor H (CFH), membrane cofactor protein (MCP), and factor I (IF)-have now been described in patients with atypical HUS. The functional effects of these mutations have been studied in detail and have been shown to affect secretion, expression, and regulatory function. Genotype-phenotype correlations have shown that the majority of patients with CFH, MCP, and FI mutations develop end-stage renal failure. The outcome of transplantation is poor in patients known to have either a CFH or FI mutation, with approximately 80% of patients losing the graft to recurrent disease within 2 years. In contrast, patients known to have only an MCP mutation have a satisfactory transplantation outcome. This is expected because MCP is a transmembrane regulator and allografts will therefore be protected by wild-type MCP. Combined liver/kidney transplantation for patients known to have a CFH mutation has not been successful to date. There is optimism that in the future, targeted complement inhibitors will be of major therapeutic benefit in this condition.

KEYWORDS

Atypical HUS - factor H - membrane cofactor protein - factor I - complement

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 Dr.
T. H. J. GoodshipProfessor 

Institute of Human Genetics, University of Newcastle upon Tyne, International Centre for Life

Newcastle upon Tyne, NE1 3BZ, United Kingdom

Email: t.h.j.goodship@ncl.ac.uk