Complete absence of the third component of complement in man

Area of Science:

• Immunology
• Complement System Biology

Background:

• Recurrent infections with encapsulated bacteria and Gram-negative organisms suggest a primary immunodeficiency.
• Complement component 3 (C3) is a central protein in both classical and alternative complement pathways, vital for opsonization, inflammation, and pathogen clearance.

Observation:

• A 4-year-old female patient presented with complete absence of total hemolytic complement and C3.
• Immune adherence was normal, but opsonic and bactericidal activities against Escherichia coli were markedly defective.
• Neutrophil migration was delayed in the Rebuck skin window test.

Findings:

• Total hemolytic complement was reconstituted upon addition of functionally pure C3.
• The patient's serum lacked antigenic C3 but contained C3b inactivator and properdin.
• Activation of the alternative pathway by inulin or cobra venom factor (CVF) was impaired, but could be restored with exogenous C3.

Implications:

• The absence of C3 significantly compromises host defense mechanisms, leading to increased susceptibility to infections.
• This case underscores the critical role of C3 in protecting against encapsulated bacteria and Gram-negative organisms.
• Understanding C3 deficiency aids in diagnosing and managing primary immunodeficiencies related to the complement system.