Complement Deficiency Syndromes

Complement deficiency is an immunodeficiency of absent or suboptimal functioning of one of the complement system proteins. Because of redundancies in the immune system, many complement disorders are never diagnosed. Some studies estimate that less than 10% are identified. ''Hypocomplementemia'' may be used more generally to refer to decreased complement levels, while ''secondary complement disorder'' means decreased complement levels that are not directly due to a genetic cause but secondary to another medical condition.

Signs and symptoms

The following symptoms (signs) are consistent with complement deficiency in general:

Complications

Vaccinations for encapsulated organisms (e.g., ''Neisseria meningitidis'' and ''Streptococcus pneumoniae'') is crucial for preventing infections in complement deficiencies. Among the possible complications are the following:
* Deficiencies of the terminal complement components increases susceptibility to infections by ''Neisseria''.

Causes

The cause of complement deficiency is genetics (though cases of an acquired nature do exist post infection). The majority of complement deficiencies are inherited as autosomal recessive conditions, while properdin deficiency occurs through X-linked inheritance. MBL deficiency can be inherited by either manner.

Inherited

* Properdin deficiency is an X-linked disorder that also causes susceptibility to ''Neisseria'' infections.
* C1-inhibitor deficiency or hereditary angioedema will have low C4 with normal C1 levels.

Acquired

Acquired hypocomplementemia may occur in the setting of bone infections (osteomyelitis), infection of the lining of the heart (endocarditis), and cryoglobulinemia. Systemic lupus erythematosus is associated with low C3 and C4. Membranoproliferative glomerulonephritis usually has low C3.

Mechanism

The mechanism of complement deficiency consists of:
* C2: In regard to C2 deficiency, about 5 different mutations in the ''C2'' gene are responsible. In turn, immune function decreases and infection opportunities increase. One of the most common mutations deletes 28 DNA nucleotides from the ''C2'' gene. Therefore, no C2 protein which can help make C3-convertase is produced. Ultimately, this delays/decreases immune response.
* C3: In terms of deficiency of C3, it has been found that 17 mutations in the ''C3'' gene cause problems with C3. This rare condition mutates or prevents C3 protein from forming, lowering the immune system's ability to protect.
* C4: C4 deficiency is highly associated with systemic lupus erythematosus. Aβ42, a protein involved in Alzheimer's disease, can cause activation of C4 (even in plasma deficient of C1q). At least one study indicates that the genetic variation of C4 plays a role in schizophrenia.

Diagnosis

The diagnostic tests used to diagnose a complement deficiency include:
* CH50 measurement
* Immunochemical methods/test
* C3 deficiency screening
* Mannose-binding lectin (lab study)
* Plasma levels/regulatory proteins (lab study)

Types

* Disorders of the proteins that act to ''inhibit'' the complement system (such as C1-inhibitor) can lead to an ''overactive'' response, causing conditions such as hereditary angioedema.
* Disorders of the proteins that act to ''activate'' the complement system (such as C3) can lead to an ''underactive'' response, causing greater susceptibility to infections.

Treatment

In terms of management for complement deficiency, immunosuppressive therapy should be used depending on the disease presented. A C1-INH concentrate can be used for angio-oedema ( C1-INH deficiency).

Pneumococcus and ''Haemophilus'' infections can be prevented via immunization. Epsilon-aminocaproic acid could be used to treat hereditary C1-INH deficiency, though the possible side effect of intravascular thrombosis should be weighed.

Epidemiology

C2 deficiency has a prevalence of 1 in about 20,000 people in Western countries.

See also

* Paroxysmal nocturnal hemoglobinuria

References

Further reading

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External links

{{Use dmy dates, date=April 2017

Noninfectious immunodeficiency-related cutaneous conditions
Syndromes