C3 Deficiency

Overview

Epidemiology

Complement component 3 (C3) deficiency is part of the larger category of complement deficiencies:

• Complement deficiencies are rare: They make up 5% of all immune deficiencies.
• Prevalence varies by geographic location.
• No gender or ethnic propensity reported.

Etiology

• Hereditary C3 deficiency:
  • Encoded on chromosome 19 by the C3 gene
  • 17 mutations in C3 gene prevent C3 protein from forming: commonly affects fragment C3b
  • Autosomal recessive inheritance
• Acquired C3 deficiency:
  • Increased consumption of C3 during infection:
    • C3 overactivation by immune complexes
    • Seen in lepromatous leprosy, bacterial endocarditis, malaria, infectious mononucleosis, dengue hemorrhagic fever, and acute hepatitis B
  • Consumption of C3 due to medical conditions:
    • Lupus
    • Membranoproliferative glomerulonephritis

Pathophysiology

• Complement cascade (3 pathways converging in common pathway):
  1. Classical pathway (C1qrs, C2, C4)
  2. Alternative pathway (C3, factor B, properdin)
  3. Lectin pathway (mannan-binding lectin (MBL))
• C3 deficiency results in malfunction of complement cascade: 
  • Decreased levels of opsonin C3b → impaired opsonization of pathogens (especially bacteria) 
  • Leads to reduced clearance of immune complexes
  • Increased risk of pyogenic bacterial infections

Diagnosis

Clinical presentation

• Recurrent bacterial infections during childhood, especially encapsulated organisms:
  • Upper respiratory tract infections
  • Pneumonia
  • Meningitis
• Generalized infections and sepsis can occur similar to Bruton agammaglobulinemia: infections with Staphylococcus, Pneumococcus, or Haemophilus influenzae
• Also associated with autoimmune diseases:
  • Systemic lupus erythematosus
  • Type III hypersensitivity reactions
  • 25% of patients develop glomerulonephritis.

Laboratory testing

Clinical testing directed by pattern of infection:

• Bacterial types
• Location of infection

Management

Management of patients with C3 deficiency centers on prevention of illness.

Prevention of infection

• Promotion of hygiene and frequent hand washing
• Monitor closely for early signs of illness.
• Vaccination: meningococcal, pneumococcal, and H. influenzae vaccines are critical.
• Prophylactic antibiotic:
  • Chronic prophylaxis is controversial.
  • May be indicated in select individuals based on severity, frequency, and kind of infection

Treatment of infection

• Antibiotic therapy directed by bacteria isolated
• Complement infusion: indicated with acute illness