Limits...
Complement regulator CD46: genetic variants and disease associations.

Liszewski MK, Atkinson JP - Hum. Genomics (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, 660 South Euclid, Saint Louis, MO, 63110, USA. kliszews@dom.wustl.edu.

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.

Show MeSH

Related in: MedlinePlus

The complement cascades. The three pathways of complement activation are shown. Although each is triggered independently, they merge at the step of C3 activation. The CP is initiated by the binding of antibody to antigen and the lectin pathway by the binding of lectin to a sugar. The alternative pathway turns over continuously and possesses a feedback loop (see Fig. 3). Activation of the complement system leads to inflammation, opsonization, and membrane perturbation. Abbreviations: MASP MBL-associated serine protease, MBL mannose-binding lectin, FB factor B, FD factor D, P properdin
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4469999&req=5

Fig2: The complement cascades. The three pathways of complement activation are shown. Although each is triggered independently, they merge at the step of C3 activation. The CP is initiated by the binding of antibody to antigen and the lectin pathway by the binding of lectin to a sugar. The alternative pathway turns over continuously and possesses a feedback loop (see Fig. 3). Activation of the complement system leads to inflammation, opsonization, and membrane perturbation. Abbreviations: MASP MBL-associated serine protease, MBL mannose-binding lectin, FB factor B, FD factor D, P properdin

Mentions: The contemporary human-complement system now consists of an efficient, interacting set of nearly 60 blood (serum) and cellular components that include components of the activating cascades, receptors, and positive and negative regulators. Complement systems similar to that in mammals also have been identified in birds, fish, amphibians, and reptiles. An AP is also found in more primitive species, even those lacking a circulatory system [13]. The complement system consists of three major activating pathways that are independently triggered, yet all have the common goal of modifying the target membrane by depositing C3 activation products and then engaging a common terminal membrane-attack complex (Fig. 2).Fig. 2


Complement regulator CD46: genetic variants and disease associations.

Liszewski MK, Atkinson JP - Hum. Genomics (2015)

The complement cascades. The three pathways of complement activation are shown. Although each is triggered independently, they merge at the step of C3 activation. The CP is initiated by the binding of antibody to antigen and the lectin pathway by the binding of lectin to a sugar. The alternative pathway turns over continuously and possesses a feedback loop (see Fig. 3). Activation of the complement system leads to inflammation, opsonization, and membrane perturbation. Abbreviations: MASP MBL-associated serine protease, MBL mannose-binding lectin, FB factor B, FD factor D, P properdin
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4469999&req=5

Fig2: The complement cascades. The three pathways of complement activation are shown. Although each is triggered independently, they merge at the step of C3 activation. The CP is initiated by the binding of antibody to antigen and the lectin pathway by the binding of lectin to a sugar. The alternative pathway turns over continuously and possesses a feedback loop (see Fig. 3). Activation of the complement system leads to inflammation, opsonization, and membrane perturbation. Abbreviations: MASP MBL-associated serine protease, MBL mannose-binding lectin, FB factor B, FD factor D, P properdin
Mentions: The contemporary human-complement system now consists of an efficient, interacting set of nearly 60 blood (serum) and cellular components that include components of the activating cascades, receptors, and positive and negative regulators. Complement systems similar to that in mammals also have been identified in birds, fish, amphibians, and reptiles. An AP is also found in more primitive species, even those lacking a circulatory system [13]. The complement system consists of three major activating pathways that are independently triggered, yet all have the common goal of modifying the target membrane by depositing C3 activation products and then engaging a common terminal membrane-attack complex (Fig. 2).Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Division of Rheumatology, Department of Medicine, Washington University School of Medicine, 660 South Euclid, Saint Louis, MO, 63110, USA. kliszews@dom.wustl.edu.

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.

Show MeSH
Related in: MedlinePlus