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

Transl Res. 2015 Feb;165(2):306-20. doi: 10.1016/j.trsl.2014.10.010. Epub 2014 Oct 20.


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 types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Atypical Hemolytic Uremic Syndrome / genetics
  • Atypical Hemolytic Uremic Syndrome / immunology
  • Atypical Hemolytic Uremic Syndrome / therapy*
  • Clinical Trials as Topic
  • Complement C5 / antagonists & inhibitors*
  • Complement Inactivating Agents / adverse effects
  • Complement Inactivating Agents / therapeutic use*
  • Female
  • Hemoglobinuria, Paroxysmal / genetics
  • Hemoglobinuria, Paroxysmal / immunology
  • Hemoglobinuria, Paroxysmal / therapy*
  • Humans
  • Male
  • Meningococcal Infections / etiology
  • Mice
  • Pregnancy
  • Translational Medical Research


  • Antibodies, Monoclonal, Humanized
  • Complement C5
  • Complement Inactivating Agents
  • eculizumab