Abstract
Membrane cofactor protein (MCP; CD46) is an ubiquitously expressed complement regulatory protein that protects host cells from injury by complement. This type-I membrane glycoprotein serves as a cofactor for the serine protease factor I to mediate inactivation of C3b and C4b deposited on host cells. More than 60 disease-associated mutations in MCP have now been identified. The majority of the mutations are linked to a rare thrombotic microangiopathic-based disease, atypical hemolytic uremic syndrome (aHUS), but new putative links to systemic lupus erythematosus, glomerulonephritis, and pregnancy-related disorders among others have also been identified. This review summarizes our current knowledge of disease-associated mutations in this complement inhibitor.
Highlights
The complement system is one of the most ancient components of innate immunity
CD46, is a member of a group of genetically, structurally, and functionally-related proteins called the regulators of complement activation (RCA) [6, 7]
60 % of atypical hemolytic uremic syndrome (aHUS) cases occur during childhood, and in a majority, the initial episode occurs before the age of 2 years
Summary
The complement system is one of the most ancient components of innate immunity. It likely evolved from a C3like protein that was cleaved by proteases into biologically active self-defense fragments to counteract invading microbes, bacteria, and to clear biologic debris (self and foreign) [1, 2]. The vertebrate-complement system consists of a set of sequentially interacting proteins featuring three major pathways that provide a swift and powerful host-defense system It promotes the inflammatory response and mediates the identification and destruction of pathogens. If a C3b lands on host cells, it must be inactivated by regulatory proteins One such control protein, CD46 (membrane cofactor protein; MCP), is a member of a group of genetically-, structurally, and functionally-related proteins called the regulators of complement activation (RCA) [6, 7]. Dysfunction of mutated proteins can result from loss-of-function (in regulators responsible for cofactor activity) or gain-of-function (activating components, hyperactive C3 convertases) Both lead to inefficiently degraded C3b and abnormal persistence of C3 and C5 convertases that, in turn, generate excessive amounts of complement-pathway effectors.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call