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Complement regulators in human disease: lessons from modern genetics
Author(s) -
Liszewski M. K.,
Atkinson J. P.
Publication year - 2015
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12338
Subject(s) - complement system , alternative complement pathway , classical complement pathway , complement membrane attack complex , complement deficiency , complement component 2 , immunology , immune system , lectin pathway , complement (music) , complement receptor , biology , antibody , phenotype , monoclonal antibody , genetics , gene , complementation
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.