Browse by author
Lookup NU author(s): Dr Veronique Fremaux-Bacchi, Professor David KavanaghORCiD
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
Hemolytic uremic syndrome (HUS) is characterized by the triad of thrombocytopenia, microangiopathic hemolytic anemia, and acute renal failure. The non-Shiga toxin-associated HUS (atypical HUS [aHUS]) has been shown to be a disease of complement dysregulation. Mutations in the plasma complement regulators factor H and factor I and the widely expressed membrane cofactor protein (MCP; CD46) have been described recently. This study looked for MCP mutations in a panel of 120 patients with aHUS. In this cohort, approximately 10% of patients with aHUS (11 patients; nine pedigrees) have mutations in MCP. The onset typically was in early childhood. Unlike patients with factor I or factor H mutations, most of the patients do not develop end-stage renal failure after aHUS. The majority of patients have a mutation that causes reduced MCP surface expression. A small proportion expressed normal levels of a dysfunctional protein. As in other studies, incomplete penetrance is shown, suggesting that MCP is a predisposing factor rather than a direct causal factor. The low level of recurrence of aHUS in transplantation in patients with MCP mutations is confirmed, and the first MCP null individuals are described. This study confirms the association between MCP deficiency and aHUS and further establishes that a deficiency in complement regulation, specifically cofactor activity, predisposes to severe thrombotic microangiopathy in the renal vasculature.
Author(s): Fremeaux-Bacchi V, Moulton EA, Kavanagh D, Dragon-Durey MA, Blouin J, Caudy A, Arzouk N, Cleper R, Francois M, Guest G, Pourrat J, Seligman R, Fridman WH, Loirat C, Atkinson JP
Publication type: Article
Publication status: Published
Journal: Journal of the American Society of Nephrology
Year: 2006
Volume: 17
Issue: 7
Pages: 2017-2025
ISSN (print): 1046-6673
ISSN (electronic): 1533-3450
Publisher: American Society of Nephrology
URL: http://dx.doi.org/10.1681/ASN.2005101051
DOI: 10.1681/ASN.2005101051
Notes: AI37618/AI/NIAID NIH HHS/United States Case Reports Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Jasn
Altmetrics provided by Altmetric
