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Hemolytic uremic syndrome: an example of insufficient complement regulation on self-tissue

Lookup NU author(s): Professor David KavanaghORCiD


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Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. HUS is classified as either diarrhea associated, most commonly caused by infection with Escherichia coli O157, or the less common atypical HUS (aHUS), which may be familial or sporadic. Approximately 50% of patients with aHUS have mutations in one of the complement control proteins: factor H, factor I, or membrane cofactor protein (MCP). These proteins regulate complement activation through cofactor activity, the inactivation of C3b by limited proteolytic cleavage, a desirable event in the fluid phase (no target) or on healthy self-tissue (wrong target). Complement activation follows the endothelial cell injury that characterizes HUS. This disease represents a model of what takes place when inappropriate complement activation occurs on self-tissues due to the presence of mutated complement regulatory proteins. Screening for mutations in factor H, factor I, or MCP is expensive and time consuming. One approach is to perform antigenic screening for factor H and factor I deficiency and to look for low levels of MCP (CD46) expression by flow cytometry. Complement regulatory protein deficiency impacts treatment decisions as patients with aHUS have a recurrence rate in renal transplants of approximately 50%, whereas those with factor H mutations have an even higher risk (approximately 80%). By contrast, MCP deficiency can be corrected in part by a renal allograft. However, caution in the use of live-related donations is needed because of the high rates of incomplete penetrance of the described mutations.

Publication metadata

Author(s): Atkinson JP, Liszewski MK, Richards A, Kavanagh D, Moulton EA

Publication type: Article

Publication status: Published

Journal: Annals of The New York Academy of Sciences

Year: 2005

Volume: 1056

Issue: 1

Pages: 144-152

ISSN (print): 0077-8923

ISSN (electronic): 1749-6632

Publisher: Wiley-Blackwell Publishing, Inc.


DOI: 10.1196/annals.1352.032

Notes: Journal Article Review United States


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