Complement regulators in human disease: Lessons from modern genetics

M. K.Liszewski, J. P. Atkinson

Research output: Contribution to journalReview article

40 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)294-305
Number of pages12
JournalJournal of Internal Medicine
Volume277
Issue number3
DOIs
StatePublished - Mar 1 2015

Keywords

  • Age-related macular degeneration
  • Atypical haemolytic uraemic syndrome
  • Complement regulation
  • Eculizumab
  • Genetics
  • Therapeutics

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