Complement Deficiency

C1 esterase inhibitor–deficiency incidence: 1:50,000-150,000 of the general population.

Symptoms onset and diagnosis occur approximately at 20 y, and by 30 y approximately 98% of pts have symptoms.

C2 deficiency incidence: <0.1% of the general population.

Male versus female ratio: 1:6.

Higher incidence (6%) in pts with autoimmune disease (see Immune Suppression).

Incidence in pts with Hx of Neisseria meningitis: 15%.

C3 and C5–C8 deficiencies have increased risk for infections.

Possible life-threatening airway compromise

Increased risk of postop infection, particularly if the deficiency affects the early complement components

Risk for inflammatory complications (e.g., glomerulonephritis, vasculitis)

Acute airway edema resulting from laryngeal or mucous membrane swelling, which can result in definitive airway obstruction; abdominal pain from intestinal edema, which may be an associated finding on exam

Increased infectious risk

Hereditary angioneurotic edema is associated with a complement deficiency of the enzyme C1 esterase inhibitor. It is a rare genetic deficiency that may lead to uncontrolled production of C2, C3, and C5 complement, resulting in acute noninflammatory, painless, nonpruritc, nonpitting edema. Initial inciting events are often the result of trauma, but may even be attributed to emotional stress.

Any component of the classical pathway, alternate pathway, or terminal common pathway may be affected.

Virtually all deficiencies show some ↑ risk of infection and/or autoimmune disease.

Deficiencies in other complement components, C2 and C3, have also been associated with immunocompromised pts, resulting in recurrent life-threatening infections associated with a variety of organisms.

Increased risk of autoimmune diseases.

Deficiency in any of the terminal components C5–C8 show selective risk of recurrent neisserial infections, which usually are not life threatening.

C1 complement results from a heterozygous deficiency of C1 esterase inhibitor. The mediators of the angioedema response result from coagulation, complement, and the kinin pathway. C1 esterase inhibitor is a key regulator for Hageman factor, coagulation, plasmin, and plasma kallikrein. There have been more than 100 mutations on the C1 esterase gene in pts without hereditary angioedema, and 20% of those have been new mutations with no prior history.

All complement proteins are inherited in an autosomal fashion, with the possible exception of properdin, which appears to be X-linked.