Learning Objective

Identify complement protein and regulatory deficiencies, their clinical manifestations, and relevant treatments.

Complement Protein Deficiencies

Early Components (C1–C4)

• Risk: Severe, recurrent pyogenic infections (sinus and respiratory).
• Additional Consequence: Impaired C3b-mediated clearance of immune complexes → increased risk of SLE.

Terminal Components (C5–C9)

• Risk: Recurrent Neisseria bacteremia.
• Mechanism: Defective MAC (C5b–C9) formation → impaired cytolysis of Neisseria.

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Complement Regulatory Protein Deficiencies

C1 Inhibitor (C1-INH) Deficiency

• Cause: Unregulated activation of kallikrein → excess bradykinin.
• Clinical Manifestation: Hereditary angioedema (swelling of face, extremities, GI tract, airway).
• Lab: Low C4 levels.
• Contraindication: ACE inhibitors (increase bradykinin).

Paroxysmal Nocturnal Hemoglobinuria (PNH)

• Cause: PIGA gene defect → defective GPI anchors → loss of complement inhibitors DAF (CD55) and MIRL (CD59).
• Pathophysiology: Complement-mediated intravascular hemolysis.
• Clinical Features:
  • Hemolysis → dark urine, low haptoglobin
  • Atypical venous thrombosis: Budd-Chiari, portal, cerebral, dermal veins
• Treatment: Eculizumab (anti-C5 antibody → inhibits terminal complement / MAC)

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