Semin Thromb Hemost 2006; 32(2): 121-127
DOI: 10.1055/s-2006-939768
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Terminal Complement Complex (C5b-9) in Children with Recurrent Hemolytic Uremic Syndrome

Friederike Prüfer1 , Johanna Scheiring1 , Sabine Sautter1 , Dorthe B. Jensen2 , Ruth Treichl2 , Reinhard Würzner2 , L. Bernd Zimmerhackl1
  • 1Universitäts-Klinik für Kinder- und Jugendheilkunde, Innsbruck, Austria
  • 2Department für Hygiene, Mikrobiologie und Sozialmedizin, Medizinische Universität Innsbruck, Innsbruck, Austria
Further Information

Publication History

Publication Date:
30 March 2006 (online)

ABSTRACT

Recurrent hemolytic uremic syndrome (recHUS) is a heterogeneous group of disorders. The pathogenesis of recHUS is not fully understood. recHUS has a high risk of development of terminal renal insufficiency and other sequelae. Abnormalities in complement factor H or in membrane-bound complement inhibitors with consecutive complement activation can be found in approximately 30 to 50% of the patients. Starting in 2001, we evaluated 42 patients with recHUS from five European countries (Germany, Austria, Hungary, Switzerland, and the Czech Republic). We measured the terminal complement complex (TCC) by an enzyme-linked immunosorbent assay using a neoepitope-specific anti-C9 antibody in 17 patients in plasma (native complement activation), serum (after coagulation), and zymosan-activated serum (Z-serum; after stimulation of coagulation). We compared the results to those of 16 healthy persons. In patients with recHUS (eight males, nine females) with a median age of 10.8 years, the TCC values were higher in plasma (0.57 versus 0.48 μg/mL; p = 0.04) and serum (3.1 versus 2.2 μg/mL) than in those of the control group, with a median age of 28.6 years (six males, 10 females) The TCC values in patients with low C3 compared with patients with normal C3 levels were even higher in plasma and serum, and the ratio was much lower. Children with recHUS have higher concentrations of TCC in plasma and serum. The ratio of Z-serum to serum showed significantly lower values in children with recHUS (96.01 versus 150.3; p = 0.01). These findings indicate a higher grade of complement activation and consumption in recHUS, suggesting that TCC may mediate cell toxicity. This may play an important role in the inferior outcome of these patients. The isolated substitution of factor H, or other complement inhibitors to block TCC formation, may represent useful therapies for these patients.

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Friederike PrüferM.D. 

Univ.-Klinik für Kinder- und Jugendheilkunde Anichstr

35, A-6020 Innsbruck, Austria

Email: friederike.pruefer@uklibk.ac.at