Complement component 3

Complement component 3, often simply called C3, is a

Deficiencies and defects of C3 result in the affected person being immunocompromised and particularly vulnerable to bacterial infections.

Function

C3 plays a central role in the activation of the complement system.^[7] Its activation is required for both classical and alternative complement activation pathways. People with C3 deficiency are susceptible to bacterial infection.^[8][9]

One form of

C3bBb is deactivated in steps. First, the proteolytic component of the convertase, Bb, is removed by complement regulatory proteins having decay-accelerating factor (DAF) activity. Next, C3b is broken down progressively to first iC3b, then C3c + C3dg, and then finally C3d. Factor I is the protease cleaves C3b but requires a cofactor (e.g Factor H, CR1, MCP or C4BP) for activity.

Structure

Several crystallographic structures of C3 have been determined^[10] and reveal that this protein contains 13 domains.^{[11][12][13][14]}
The C3 precursor protein is first processed by the removal of 4 Arginine residues, forming two chains, beta and alpha, linked by a disulfide bond. The C3 convertase activates C3 by cleaving the alpha chain, releasing C3a anaphylatoxin and generating C3b (beta chain + alpha' (alpha prime) chain).

Biochemistry

Biosynthesis

In humans, C3 is predominantly synthesised by liver hepatocytes^[5] and to some degree by epidermis keratinocytes.^[15]

Clinical use

Levels of C3 in the blood may be measured to support or refute a particular medical diagnosis. For example, low C3 levels are associated with Systemic Lupus Erythematosus (SLE)^[16] and some types of kidney disease such as

Factor H is the primary regulator of C3. Deficiency of Factor H may lead to uncontrolled C3 activity through the alternative pathway of the complement system.^[17]

Pathology

Deficiency of C3 results in the affected person being immunocompromised. Specifically, they are vulnerable to bacterial pathogens, including repeat infections by the same organism, but are not susceptible to viruses. This vulnerability also occurs in an individual deficient in C1, C2, C4, or any of their required components or associated proteins, and the clinical effects are very similar regardless of the specific deficiency. This is because all of these must work with C3 for the complement system to function.^[18]

Affected people are particularly vulnerable to infections with Gram-negative organisms such as pathogenic E. coli or Salmonella enterica.^[19] Additionally, C3 and other complement deficiencies are associated with frequent and severe respiratory infections, as well as other infections that invade and penetrate tissue layers.^[18]

Some data shows that acquired C3 deficiency, including when this is intentionally done for medical immunosuppression purposes, may not significantly impact a person's immune function long-term.^[20] However, by contrast, congenital C3 deficiency is known to cause chronic illness.^[18]

Additionally, several forms of C3 deficiency contribute to the development of systemic lupus erythematosus and other autoimmune diseases.^[18]

References