Description

• Complement is a major component of the innate immune system.
  • Consists of plasma and membrane proteins which mediate three pathways of cascading enzyme reactions (classical, alternative, and lectin pathways)
  • Pathway activation leads to inflammatory and immune responses.
• Deficiencies can arise in any of the proteins, leading to loss of activity of the deficient protein as well as loss of function of proteins that follow in the cascade.
• Inherited deficiencies of the complement components may predispose individuals to bacterial infections and autoimmunity.
• Secondary/acquired deficiencies are much more common than inherited deficiencies and are most often caused by increased consumption by immune complexes.

Epidemiology

• Complement deficiency accounts for 1–6% of all primary immune deficiencies (PIDs); up to 10% in some registries.
• Homozygous C2 deficiency 1 in 20,000
• Partial C4 deficiency in 1–3% of Caucasian population
• C9 deficiency almost always found in people of Japanese descent
• C6 deficiency more common in African Americans
• Alternative pathway deficiencies (properdin, factor D) are rare.

Risk Factors

Pathophysiology

• Classic complement pathway is activated when IgM or IgG antibodies bind to antigen.
• Lectin pathway is activated when a serum lectin such as mannose-binding lectin (MBL) binds to antigen.
• Alternative pathway does not need antibody or lectins to be activated.
• Main goal of all three pathways is to deposit C3b fragments on the target antigen to mark the target for immune response.

Etiology

• Primary complement deficiencies are hereditary.
• Acquired deficiencies: accelerated consumption by immune complexes (most common), decreased hepatic production (less common), or loss through the urine (rare)