Complement component 8 deficiency
Complement component 8 deficiency is a rare immunodeficiency disorder that impairs the immune system's ability to protect the body, significantly increasing the risk of recurrent bacterial meningitis.
Overview
Complement component 8 deficiency is a disorder that causes the immune system to malfunction, resulting in a form of immunodeficiency. Immunodeficiencies are conditions in which the immune system is unable to protect the body effectively from foreign invaders such as bacteria. The severity of complement component 8 deficiency varies widely; while some individuals experience multiple infections, others do not develop any health problems related to the disorder.
Symptoms & Clinical Features
People with complement component 8 deficiency have a significantly increased risk of recurrent bacterial infections, particularly by a bacterium called Neisseria meningitidis. Key clinical aspects include:
- Inflammation of the membranes surrounding the brain and spinal cord (meningitis) caused by Neisseria meningitidis infection
- Although meningitis can be life-threatening, individuals with complement component 8 deficiency are statistically less likely to die from the infection than individuals in the general population who contract it
There are two types of complement component 8 deficiency, types I and II, classified by their genetic cause. Both types present with the same signs and symptoms.
Frequency
Complement component 8 deficiency is a rare disorder, though its exact prevalence is unknown. The two types show different population distributions:
- Type I occurs in several populations, particularly in people of Hispanic, Japanese, or African Caribbean heritage.
- Type II primarily occurs in people of Northern European descent.
Causes & Genetic Factors
Complement component 8 deficiency is caused by mutations in either the C8A or C8B gene. Mutations in the C8A gene cause type I, while mutations in the C8B gene cause type II. These genes provide instructions for making pieces of a protein complex called complement component 8. This complex is composed of:
- An alpha subunit (produced from the C8A gene)
- A beta subunit (produced from the C8B gene)
- A gamma subunit (produced from the C8G gene)
Complement component 8 is a key player in the complement system, a group of proteins that work together to destroy foreign invaders, trigger inflammation, and clear cellular debris. Complement component 8 combines with other complement proteins to form the membrane attack complex (MAC). The MAC inserts itself into the outer membrane of bacterial cells, creating a pore that kills the bacterium.
Mutations in C8A or C8B lead to a shortage of the respective subunit, which impairs the formation of complement component 8. Without this component, the membrane attack complexes cannot form, leaving the body's immune response impaired, particularly against Neisseria meningitidis, and making affected individuals prone to recurrent meningitis.
Associated Genes
- C8A
- C8B
Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Other Names for This Condition
- C8 deficiency