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 not able to protect the body effectively from foreign invaders such as bacteria. People with complement component 8 deficiency have a significantly increased risk of recurrent bacterial infections, particularly by a bacterium called Neisseria meningitidis. Infection by this bacterium causes inflammation of the membranes surrounding the brain and spinal cord (meningitis). Although meningitis can be life-threatening, individuals with complement component 8 deficiency are less likely to die from the infection than people in the general population who contract it.

The severity of complement component 8 deficiency varies widely. While some people with this condition experience one or more infections, others do not have any health problems related to the disorder.

There are two types of complement component 8 deficiency, types I and II, classified by their genetic cause. The two types have the same signs and symptoms.

Complement component 8 deficiency is caused by mutations in the C8A or C8B gene. C8A gene mutations underlie type I, and C8B gene mutations 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, and a gamma subunit, produced from another gene called C8G.

Complement component 8 aids in a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Complement component 8 combines with several other complement proteins to form the membrane attack complex (MAC), which inserts itself in the outer membrane of bacterial cells. This complex creates a hole (pore) in the membrane, which kills the bacterium.

Mutations in either C8A or C8B lead to a shortage of the respective subunit, which impairs formation of complement component 8. Without complement component 8, membrane attack complexes cannot form, which impairs the immune response, particularly against Neisseria meningitidis. This impaired immune response leaves affected individuals prone to recurrent episodes of meningitis.

Normal Function

The C8A gene provides instructions for making one piece, the alpha subunit, of a protein complex called complement component 8. The alpha subunit is linked to another piece of the complex called the gamma subunit (produced from the C8G gene). These two proteins interact with the beta subunit (produced from the C8B gene) to form complement component 8.

Complement component 8 aids in a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Complement component 8 combines with several other complement proteins to form the membrane attack complex (MAC), which inserts itself in the outer membrane of bacterial cells. This complex creates a hole (pore) in the membrane, which kills the bacterium. This part of the immune response appears to be especially important for fighting infection by bacteria in the Neisseria genus.

Health Conditions Related to Genetic Changes

Complement component 8 deficiency

At least two mutations in the C8A gene have been found to cause complement component 8 deficiency type I. This condition is an immune system disorder, known as an immunodeficiency, in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria. People with complement component 8 deficiency have a significantly increased risk of developing recurrent infections, particularly by Neisseria meningitidis, which causes meningitis, a serious condition that involves inflammation of the membranes surrounding the brain and spinal cord.

Mutations in the C8A gene alter the blueprint for protein production; if produced, the abnormally short alpha subunit is likely broken down quickly. The resulting shortage of this protein impairs formation of complement component 8. Deficiency of this component prevents formation of membrane attack complexes. Without this part of the immune response, affected individuals are prone to infection, particularly by Neisseria bacteria.

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Other Names for This Gene

• complement component 8 alpha subunit
• complement component 8 subunit alpha
• complement component 8, alpha polypeptide
• complement component C8 alpha chain preproprotein

Genomic Location

Normal Function

The C8B gene provides instructions for making one piece, the beta subunit, of a protein complex called complement component 8. To form this complex, the beta subunit interacts with another piece made up of the alpha subunit (produced from the C8A gene) and the gamma subunit (produced from the C8G gene), which are linked.

Complement component 8 aids in a part of the body's immune response known as the complement system. The complement system is a group of proteins that work together to destroy foreign invaders, trigger inflammation, and remove debris from cells and tissues. Complement component 8 combines with several other complement proteins to form the membrane attack complex (MAC), which inserts itself in the outer membrane of bacterial cells. This complex creates a hole (pore) in the membrane, which kills the bacterium. This part of the immune response appears to be especially important for fighting infection by bacteria in the Neisseria genus.

Health Conditions Related to Genetic Changes

Complement component 8 deficiency

Several mutations in the C8B gene cause complement component 8 deficiency type II. This condition is an immune system disorder, known as an immunodeficiency, in which the immune system is not able to protect the body effectively from foreign invaders such as bacteria. People with complement component 8 deficiency have a significantly increased risk of developing recurrent infections, particularly by Neisseria meningitidis, which causes meningitis, a serious condition that involves inflammation of the membranes surrounding the brain and spinal cord.

C8B gene mutations involved in complement component 8 deficiency are most often of a type called a C to T transition, in which a DNA building block (nucleotide) called cytosine (C) is changed to the nucleotide thymine (T). Most commonly, this change occurs in a region of the gene called exon 9, but it can occur in other regions. These mutations alter the sequence of protein building blocks, resulting in an abnormally short protein that, if produced, is likely broken down quickly. Other types of mutations can occur in the C8B gene; they also lead to an abnormally short protein that is quickly broken down. The resulting shortage of this protein impairs formation of complement component 8. Deficiency of this component prevents formation of membrane attack complexes. Without this part of the immune response, affected individuals are prone to infection, particularly by Neisseria bacteria.

Other Names for This Gene

• C82
• complement component 8 subunit beta
• complement component 8, beta polypeptide
• complement component C8 beta chain isoform 1 preproprotein
• complement component C8 beta chain isoform 2
• complement component C8 beta chain isoform 3

Genomic Location

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.

Complement component 8 deficiency is a rare disorder, although its prevalence is unknown. Type I occurs in several populations, particularly in people with Hispanic, Japanese, or African Caribbean heritage, whereas type II primarily occurs in people of Northern European descent.