Complement C4 test: what the result means

Complement C4 is one of the nearly 60 proteins that make up the complement system — the part of the immune system that helps the body fight infections and clear damaged cells. C4 takes part in the classical pathway of complement activation: when complexes of antibodies and antigens form in the body (for example in an autoimmune disease), C4 is used up to activate this pathway, so its level in the blood falls.

For this reason C4 (together with C3) is most often tested not as a single marker but as part of the diagnosis and monitoring of autoimmune diseases — especially systemic lupus erythematosus (lupus). A complement test also helps to assess some infections and a rare inherited condition — angioedema, in which one of the complement system proteins is lacking. Because the C4 level reflects how much of the complement system is currently being “used up” during an immune response, it is often repeated over time in order to follow disease activity or how well treatment is working.

• When systemic lupus erythematosus (lupus) or another autoimmune disease is suspected, with joint pain, a rash, fatigue or other characteristic symptoms
• To monitor the activity of already diagnosed lupus or rheumatoid arthritis, and how well treatment is working, over time
• When recurring bacterial infections of unclear cause are suspected
• When inherited angioedema is suspected — when unexplained swelling of the skin or mucous membranes keeps coming back
• When assessing liver diseases or kidney diseases, if the doctor wants to clarify the state of the immune system
• Together with C3 and other autoimmune markers, when a wider picture of an autoimmune disease is being built

The overall numerical interval depends on the laboratory's method, so you will find the exact reference range on your own result sheet. What matters is not a single value so much as the change over time — especially in people with autoimmune diseases, in whom C4 is measured repeatedly.

A raised C4 may indicate an inflammatory process in the body, certain malignant diseases (for example leukaemia or non-Hodgkin lymphoma) or an inflammatory bowel disease such as ulcerative colitis. In people with lupus, a raised complement level during monitoring sometimes shows that treatment is working effectively. Other blood tests and the clinical picture help to establish the specific cause.

• An inflammatory process in the body (complement is an acute phase protein)
• Some malignant diseases, for example leukaemia or non-Hodgkin lymphoma
• Ulcerative colitis — inflammation of the lining of the bowel
• In lupus — a rise during monitoring may show that treatment is working

What is usually assessed together with a raised result:

• Discussing the overall clinical picture and other inflammation markers with the doctor (CRP, ESR)
• If lupus or rheumatoid arthritis is present — assessing the result together with monitoring of disease activity
• Repeating the test over time, if the doctor sees a reason to follow the change

A lowered C4: what it may mean

A lowered C4 is most often linked with autoimmune diseases — systemic lupus erythematosus (lupus) and rheumatoid arthritis are the most common causes, because complement is used up during the immune response. Other causes are cirrhosis of the liver, certain kidney diseases, inherited angioedema, poor nutrition or recurring bacterial infections.

• Systemic lupus erythematosus (lupus) and rheumatoid arthritis
• Cirrhosis of the liver
• Certain kidney diseases
• Inherited angioedema — a rare form of immune system disorder
• Poor nutrition
• Recurring bacterial infections

What is usually assessed together with a lowered result:

• Discussing the possibility of an autoimmune disease with the doctor, especially if there is joint pain or a rash
• Assessing it together with C3 and other autoimmune tests for a wider picture
• If angioedema is suspected — consulting about the specific further tests
• Repeating the test, if the doctor is following the activity of lupus or another autoimmune disease over time