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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.
The mechanism of complement deficiency consists of:
* C2: In regard to complement component 2, 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 complement component 3, 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: complement component 4, C4 deficiency is highly associated with systemic lupus erythematosus. Amyloid beta, 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.
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 complement component 3, C3) can lead to an ''underactive'' response, causing greater susceptibility to infections.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 osteomyelitis, bone infections (osteomyelitis), endocarditis, infection of the lining of the heart (endocarditis), and cryoglobulinemia. Systemic lupus erythematosus is associated with low Complement component 3, C3 and Complement component 4, C4. Membranoproliferative glomerulonephritis usually has low C3.Mechanism
The mechanism of complement deficiency consists of:
* C2: In regard to complement component 2, 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 complement component 3, 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: complement component 4, C4 deficiency is highly associated with systemic lupus erythematosus. Amyloid beta, 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 * Immunochemistry, Immunochemical methods/test * Complement component 3, C3 deficiency screening * Mannose-binding lectin (lab study) * Blood plasma, Plasma levels/regulatory proteins (lab study)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 hemoglobinuriaReferences
Further reading
* *External links
{{Authority control Complement deficiency, Noninfectious immunodeficiency-related cutaneous conditions Syndromes