Complement Disorders: Pathological High-Yield
The complement system is a key part of the innate immune response, facilitating opsonization, chemotaxis, and direct pathogen lysis. Deficiencies in this system lead to specific clinical patterns based on which pathway or component is affected.
1. Clinical Pattern Recognition
| Deficiency | Clinical Significance |
|---|---|
| C1, C2, C4 Deficiency | Associated with an increased risk of SLE and other immune-complex diseases. |
| C5-C9 Deficiency | Increased susceptibility to recurrent infections with Neisseria species (meningococcus/gonococcus). |
| C1 Esterase Inhibitor Deficiency | Causes Hereditary Angioedema. Characterized by excessive bradykinin production; avoid ACE inhibitors. |
2. Critical Board Exam Concepts
- Hereditary Angioedema (HAE): Deficiency in C1 esterase inhibitor leads to unregulated activation of the classical pathway and excessive production of bradykinin. Clinical features include recurrent skin swelling and life-threatening laryngeal edema. Do not use ACE inhibitors, as they increase bradykinin levels.
- Paroxysmal Nocturnal Hemoglobinuria (PNH): Caused by a defect in the PIG-A gene, which leads to the absence of GPI anchors for membrane proteins like DAF (CD55) and MIRL (CD59). These proteins normally inhibit complement-mediated lysis of RBCs. The result is intravascular hemolysis.
- Complement Functions:
- C3b: Primary opsonin (promotes phagocytosis).
- C3a, C4a, C5a: Anaphylatoxins (trigger mast cell degranulation and inflammation).
- C5a: Powerful chemotactic factor for neutrophils.
3. Diagnostic Pearls
Pathology Pearl: To screen for total complement activity, check the CH50 test. It measures the ability of a patient’s serum to lyse 50% of antibody-sensitized sheep erythrocytes. A low CH50 indicates a deficiency in one or more of the classical pathway components.