C3, C4 and C1 are proteins that form part of the complement system, an essential component of the innate immune system. The complement system helps the body eliminate pathogens, damaged cells and foreign substances, while also supporting the body’s overall immune response.
Testing these proteins is valuable for diagnosing disease, monitoring treatment, and assessing disease activity, particularly in autoimmune diseases, immune-mediated kidney disorders, and conditions involving abnormalities of the complement system.
What is C3 (Complement Component 3)?
C3 is the most important protein in the complement system and plays a central role in all complement activation pathways.
Why is C3 measured?
A C3 test is used to:
- Assess the function of the complement system
- Help diagnose and monitor autoimmune diseases, such as systemic lupus erythematosus (SLE)
- Evaluate immune-mediated kidney diseases, including lupus nephritis and glomerulonephritis
- Help assess certain severe infections and excessive complement consumption
Low C3 levels may be seen in:
- Active systemic lupus erythematosus (SLE)
- Immune-mediated kidney disease
- Certain severe infections
- Congenital C3 deficiency (rare)
What is C4 (Complement Component 4)?
C4 is involved in the classical and lectin pathways of the complement system. It is commonly measured alongside C3 to provide a more complete assessment of complement activity.
Why is C4 measured?
A C4 test is used to:
- Help diagnose autoimmune diseases
- Monitor disease activity in SLE when interpreted together with C3
- Assess diseases associated with immune complex deposition
Low C4 levels may be seen in:
- Systemic lupus erythematosus (SLE)
- Certain autoimmune diseases
- Congenital C4 deficiency (rare)
What is C1 Esterase Inhibitor (C1-INH)?
In clinical practice, testing C1 generally refers to measuring C1 Esterase Inhibitor (C1-INH), a protein that regulates both the complement system and inflammatory pathways, preventing excessive immune activation.
Why is C1-INH measured?
A C1-INH test is used to:
- Diagnose hereditary angioedema (HAE) caused by C1-INH deficiency or dysfunction
- Distinguish non-allergic causes of recurrent swelling
- Assess acquired angioedema
People with hereditary angioedema (HAE) commonly experience:
- Swelling of the face, lips, tongue, hands, feet or genitals
- Abdominal pain caused by swelling of the intestinal wall
- No hives (urticaria) or itching
- Swelling of the larynx, which can obstruct the airway and become a life-threatening medical emergency
What Does Each Test Assess?
C3
- Complement system function
- Autoimmune diseases
- Immune-mediated kidney disease
- Certain severe infections
C4
- Autoimmune diseases, particularly systemic lupus erythematosus (SLE)
- Disorders associated with immune complex deposition
C1 Esterase Inhibitor (C1-INH)
- Hereditary angioedema (HAE)
- Acquired angioedema
Who Should Be Tested?
C3 and C4 are not routine health screening tests for the general population. They are usually requested when there are specific clinical indications, such as:
- Suspected autoimmune disease, particularly SLE
- Suspected immune-mediated kidney disease
- Chronic inflammation of unknown cause
- Suspected disorders involving abnormal complement activation or consumption
C1-INH testing is generally recommended for people who experience recurrent episodes of swelling without hives, or when hereditary angioedema (HAE) is suspected. It is often performed alongside a C4 test to improve diagnostic accuracy.
Summary
Testing C3, C4 and C1 Esterase Inhibitor (C1-INH) provides a specialised assessment of the complement system and immune function. These tests play an important role in diagnosing and monitoring autoimmune diseases, immune-mediated kidney disorders, and angioedema caused by complement system abnormalities.
These investigations should be performed only when clinically indicated, based on a person’s symptoms, medical history and physical examination. They are not recommended as routine screening tests for the general population.
