What is C4?
C4 refers to the fourth component of the
complement system, a key part of the immune system. The complement system consists of a series of small proteins that enhance the ability of
antibodies and
phagocytic cells to clear pathogens from an organism. C4 plays a crucial role in both the
classical and
lectin pathways of complement activation.
What is the Structure of C4?
C4 is a large glycoprotein composed of three polypeptide chains: alpha, beta, and gamma. These chains are encoded by a single gene and are assembled into a functional protein through a complex process of
post-translational modifications. The native C4 protein is cleaved into two fragments, C4a and C4b, upon activation. C4b plays a key role in the formation of the
C3 convertase enzyme complex.
How is C4 Activated?
C4 activation involves cleavage by
C1s, a serine protease that is part of the C1 complex in the classical pathway, or by
MASPs in the lectin pathway. Once activated, C4 is split into C4a and C4b. C4a is an anaphylatoxin that can cause inflammation, while C4b binds covalently to the pathogen surface, forming a platform for further complement activation.
What is the Role of C4 in the Immune Response?
C4 is essential for the formation of the C3 convertase complex, which is necessary for the amplification of the complement cascade. C3 convertase cleaves C3 into C3a and C3b, leading to a cascade of events that result in opsonization, cell lysis, and inflammation. By facilitating these processes, C4 helps the immune system to effectively target and eliminate pathogens.What are the Clinical Implications of C4 Deficiency?
C4 deficiency can lead to increased susceptibility to infections and autoimmune diseases. For instance, individuals with C4 deficiency are at higher risk for developing
Systemic Lupus Erythematosus (SLE), an autoimmune disease characterized by the body's immune system attacking its own tissues. The lack of C4 impairs the ability of the immune system to clear immune complexes, which can deposit in tissues and cause inflammation.
How is C4 Measured in the Laboratory?
In a clinical setting, C4 levels can be measured using various techniques such as
nephelometry or
ELISA. These assays help in diagnosing immune deficiencies and monitoring the activity of autoimmune diseases. Low levels of C4 can indicate a deficiency or excessive consumption due to ongoing immune activation.
Recent Advances in C4 Research
Recent studies have focused on the genetic aspects of C4, including the discovery of
copy number variations (CNVs) in the C4 gene. These variations can influence the amount of C4 protein produced and have been linked to susceptibility to autoimmune diseases. Ongoing research aims to better understand the regulatory mechanisms controlling C4 expression and its impact on immune function.
