From the Guidelines
A low C4 (complement component 4) level indicates activation of the classical complement pathway, which is commonly seen in autoimmune diseases, particularly systemic lupus erythematosus (SLE) and lupus nephritis, as well as in hereditary angioedema due to genetic deficiency of C1 inhibitor. When interpreting low C4 results, it's essential to consider the clinical context and other laboratory findings. Some key points to consider include:
- Low C4 levels can be seen in various conditions, including autoimmune diseases, hereditary angioedema, and immune complex-mediated diseases 1.
- In autoimmune diseases, low C4 levels often suggest ongoing disease activity and may help guide treatment decisions 1.
- In hereditary angioedema, low C4 is due to genetic deficiency of C1 inhibitor rather than consumption 1.
- C4 levels should be monitored over time rather than as a single measurement to assess disease activity and treatment response 1.
- Measuring C4 levels is recommended as the best initial screening test to exclude a diagnosis of hereditary angioedema 1.
- A normal C4 level during an attack of hereditary angioedema strongly suggests that a diagnosis of hereditary angioedema is unlikely 1. It is crucial to consider the clinical context and other laboratory findings when interpreting low C4 results, as the same laboratory result can have different implications in different clinical scenarios 1.
From the Research
Low C4 Complement Level Indications
A low C4 (complement component 4) level can indicate several conditions, including:
- Systemic lupus erythematosus (SLE) 2, 3
- Hereditary angioedema (HAE) 4, 5
- Complement deficiency 6, 2
- Immune complex-mediated diseases 3
Association with Systemic Lupus Erythematosus
Low C4 levels have been strongly associated with SLE, particularly in patients with complete deficiencies of complement components C4A and C4B 2. Studies have shown that heterozygous and homozygous deficiencies of C4A are present in 40-60% of SLE patients from various ethnic groups 2.
Diagnostic Value
Low serum complement C3 and C4 levels have been proposed as immunologic criteria to enhance the sensitivity of SLE classification criteria 3. The diagnostic value of low C3 and C4 levels in Chinese patients with SLE has been evaluated, showing that simultaneously low C3 and C4 levels are highly prevalent in SLE patients 3.
Complement Deficiency
Complement deficiencies, including C4 deficiency, can increase the risk of developing SLE and other immune complex-mediated diseases 6, 2. The usual measurements of CH50, C3, and C4 levels may not be adequate to detect a C4 and/or C2 deficiency in patients with LE 6.
Hereditary Angioedema
Low C4 levels have also been observed in patients with hereditary angioedema, particularly those with uncontrolled angioedema 4. Measures that limit hypocomplementaemia in HAE may reduce the incidence of secondary SLE 4.