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Anticomplement C5 therapy with eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome

Lookup NU author(s): Dr Edwin Wong, Professor David KavanaghORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


The complement inhibitor eculizumab is a humanized monoclonal antibody against C5. It was developed to specifically target cleavage of C5 thus preventing release of C5a and activation of the terminal pathway. Paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) are 2 diseases with distinctly different underlying molecular mechanisms. In PNH, progeny of hematopoietic stem cells that harbor somatic mutations lead to a population of peripheral blood cells that are deficient in complement regulators resulting in hemolysis and thrombosis. In aHUS, germline mutations in complement proteins or their regulators fail to protect the glomerular endothelium from complement activation resulting in thrombotic microangiopathy and renal failure. Critical to the development of either disease is activation of the terminal complement pathway. Understanding this step has led to the study of eculizumab as a treatment for these diseases. In clinical trials, eculizumab is proven to be effective and safe in PNH and aHUS.

Publication metadata

Author(s): Wong EKS, Kavanagh D

Publication type: Review

Publication status: Published

Journal: Translational Research

Year: 2015

Volume: 165

Issue: 2

Pages: 306-320

Print publication date: 01/02/2015

Online publication date: 20/10/2014

Acceptance date: 16/10/2014

ISSN (print): 1931-5244

ISSN (electronic): 1878-1810



DOI: 10.1016/j.trsl.2014.10.010