Complement Deficiencies

Complement is a series of circulating enzymatic serum proteins with nine functional components, labeled C1 through C9. Complement deficiency or dysfunction may increase susceptibility to infection and seems to be related to certain autoimmune disorders.

Theoretically, any complement component may be deficient or dysfunctional, and many such disorders are under investigation. Primary complement deficiencies are rare. The most common are C1 , C2, and C4 deficiencies, and C5 familial dysfunction.

More common secondary complement abnormalities have been confirmed in patients with lupus erythematosus, in some with dermatomyositis, in one with scleroderma (and in his family), and in a few patients with gonococcal and meningococcal infections.

Some disorders associated with secondary deficiencies of complement are asplenia, sickle cell anemia, protein-deficient status, acute nephritis, immune complex disease, and bacteremia.

The prognosis varies with the abnormality and the severity of associated diseases.

Causes

Primary complement deficiencies are inherited as autosomal recessive traits, except for deficiency of C1 esterase inhibitor, which is autosomal dominant. Secondary deficiencies may follow complement-fixing (complement-consuming) immunologic reactions, such as drug-induced serum sickness, acute streptococcal glomerulonephritis, asplenia, sickle cell anemia, acute nephritis, bacteremia, and acute active systemic lupus erythematosus.

Normally, immunoglobulin (lg) G or IgM reacts with antigens as part of an immune response, activating C1, which then combines with C4, initiating the classical complement pathway, or cascade. (An alternative complement pathway involves the direct activation of C3 by the serum protein properdin, bypassing the initial components [C1, C2, and C4] of the classical pathway.) Complement then combines with the antigen-antibody complex and undergoes a sequence of complicated reactions that amplify the immune response against the antigen. This complex process is called complement fixation. Any deficiency in complement interferes with this system.

Symptoms

Symptoms vary depending on the specific complement deficiency and the disease that results. Some people remain healthy with no symptoms at all. Others, who suffer from frequent infections, may develop a high fever, headaches, diarrhea , with a stiff neck, or a cough with chest pain .

If an autoimmune disease develops, like lupus, the person may lose weight, suffer from a rash, and have joint pain. Other symptoms of complement deficiency diseases (like hereditary angioedema, paroxysmal nocturnal hemoglobinuria, or leukocyte adhesion deficiency syndrome) include abdominal and back pain, skin infections, edema or swelling of the face and red bumps on the skin.

Diagnostic tests

Diagnosis of a complement deficiency is difficult and requires careful interpretation of both clinical features and laboratory results. Various complement deficiencies cause a low total serum complement level (CH50). Specific assays may help to confirm deficiency of specific complement components. For example, immunofluorescence of glomerular tissues in glomerulonephritis that reveals complement components and IgG strongly suggests complement deficiency.

Treatment

Although primary complement deficiencies have no known cure, the associated infections, collagen vascular disease, and renal disease require prompt treatment. Transfusion of fresh frozen plasma replaces complement components, but this treatment is controversial because it doesn't cure complement deficiencies and provides only transient beneficial effects. Although helpful, bone marrow transplantation can cause potentially fatal graft-versus-host disease (GVHD). Anabolic steroids and antifibrinolytic agents reduce acute swelling in patients with C1 esterase inhibitor deficiency. Primary management consists of antibiotic therapy and prophylaxis.

Prevention

There is currently no way to prevent complement deficiencies.

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