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.

Types

Signs and symptoms

The following symptoms (signs) are consistent with complement deficiency in general: • Recurring infection • Auto-immune disorders • Glomerulonephritis • Joint problems (manifestation) • Lung function (MBL variant alleles) • Angioedema • Dermatomyositis • Vasculitis • Anaphylactoid purpura

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:

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

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:

Diagnosis

The diagnostic tests used to diagnose a complement deficiency include:

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.