Complement regulators in human disease: lessons from modern genetics

• Autores: M. Kathryn Liszewski , John P. Atkinson
• Localización: Journal of Internal Medicine, ISSN-e 1365-2796, Vol. 277, Nº. 3, 2015, págs. 294-305
• Idioma: inglés
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• Resumen

  • First identified in human serum in the late 19th century as a ‘complement’ to antibodies in mediating bacterial lysis, the complement system emerged more than a billion years ago probably as the first humoral immune system. The contemporary complement system consists of nearly 60 proteins in three activation pathways (classical, alternative and lectin) and a terminal cytolytic pathway common to all. Modern molecular biology and genetics have not only led to further elucidation of the structure of complement system components, but have also revealed function-altering rare variants and common polymorphisms, particularly in regulators of the alternative pathway, that predispose to human disease by creating ‘hyperinflammatory complement phenotypes’. To treat these ‘complementopathies’, a monoclonal antibody against the initiator of the membrane attack complex, C5, has received approval for use. Additional therapeutic reagents are on the horizon.