Complement disorders affect the complement proteins that make up the complement system, which helps clear pathogens through opsonisation, inflammation and direct cell lysis. Complement proteins are particularly important in dealing with encapsulated organisms, such as:
- Haemophilus influenzae type b (Hib)
- Streptococcus pneumoniae
- Neisseria meningitidis
Complement Deficiencies
Key complement deficiencies include:
- C2 deficiency (the most common and associated with respiratory tract, ear and throat infections)
- C5-C9 deficiency (associated with recurrent Neisseria infections, e.g., meningococcal disease)
- C4 deficiency (associated with systemic lupus erythematosus)
Complement deficiencies, particularly C4 deficiency, are also associated with immune complex disorders, such as systemic lupus erythematosus. An incomplete complement cascade results in the formation of immune complexes that are deposited in tissues, causing chronic inflammation.
Vaccination against encapsulated organisms is important in patients with complement deficiencies. In some cases, antibiotic prophylaxis is used.
Hereditary Angioedema
Hereditary angioedema, also called C1 esterase inhibitor deficiency, involves deficiency or abnormal functioning of C1 esterase inhibitor. Deficiency leads to excessive bradykinin.
Bradykinin is released during the inflammatory response. It is responsible for promoting blood vessel dilatation and increased vascular permeability, leading to angioedema.
Hereditary angioedema causes intermittent episodes of angioedema. These episodes may occur in response to minor triggers, such as viral infections or stress, or without a clear trigger. Exogenous oestrogen (e.g., the combined pill) can make attacks more frequent or severe.
Angioedema often affects the lips or face but can also affect the tongue, airway, hands, feet, genitals, or GI tract. Laryngeal angioedema can compromise the airway. The swelling often lasts 2-5 days before resolving spontaneously.
Short-term treatment options include:
- Intravenous C1 esterase inhibitor (as prophylaxis before procedures or in response to attacks)
- Subcutaneous icatibant (in response to attacks)
TOM TIP: The initial test for hereditary angioedema is to check C4 levels, which are low in the condition. The exam question may describe a patient with episodes of unexplained lip swelling and ask what test to perform. The answer is C4 levels. This would be followed by testing the C1 inhibitor level and function.
Mannose-Binding Lectin Deficiency
Genetic deficiency in mannose-binding lectin (MBL) is relatively common. Mannose-binding lectin binds to mannose on the surface of pathogens and activates the complement system. Deficiency in mannose-binding lectin leads to impaired activation of the lectin pathway of the complement system.
In otherwise healthy individuals, mannose-binding lectin deficiency typically does not cause problems. Some patients can experience more frequent respiratory infections. It may worsen outcomes in patients with conditions involving recurrent infections (e.g., cystic fibrosis and bronchiectasis).
Last updated April 2026
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