C4

C4 is a protein in the complement system, part of the immune system that helps antibodies and defence cells remove microorganisms and damaged cells. It is most often tested alongside the C3 component for suspected systemic lupus and certain kidney diseases, and when investigating recurrent swelling suggesting hereditary angioedema.

Who the test is for

• people with suspected systemic lupus erythematosus (SLE) and those receiving treatment, particularly with kidney involvement;
• people being investigated for inflammation of the kidney filtering units (glomerulonephritis) or cryoglobulinaemia;
• people with recurrent swelling of the skin, face, lips or throat or attacks of severe abdominal pain without hives, when hereditary angioedema is suspected;
• less often, people with frequent or severe bacterial infections when a doctor is investigating complement deficiency.

What C4 is and what it indicates

Complement consists of around thirty proteins activated in blood one after another, like a chain. C4 participates in the classical activation pathway, most often triggered by antibodies bound to foreign substances or the body’s own cells.

When complement is strongly or persistently activated, for example in immune-complex autoimmune diseases, C4 is consumed and its blood level falls. In inflammation the liver produces more complement, so C4 can be mildly elevated. A low result is therefore usually more important to a doctor than elevated C4.

The test is not part of a routine check-up or a general assessment of immunity. It is performed for a specific reason, most often on a rheumatologist’s, nephrologist’s, immunologist’s or allergist’s recommendation.

Preparation and sample

C4 is measured in venous blood and fasting is not required. Tell your doctor which medicines you take and whether you recently had an infection, because inflammation can change complement levels.

How results are interpreted

C4 is expressed in g/L. The reference interval depends on the method and is printed on the report. A doctor interprets results, most often alongside C3, together with symptoms and other tests.

Result	What it may mean
low C4 and low C3	complement consumption, for example in active lupus or immune-complex disease
low C4, normal C3	hereditary angioedema, cryoglobulinaemia or an inherited lower C4 level
normal C4, low C3	complement activation through another pathway, for example kidney inflammation after streptococcal infection
mildly high C4	inflammation or infection; usually no particular significance alone

Some people inherit fewer copies of the C4 gene and have persistently somewhat lower C4 without disease. Complete inherited C4 deficiency is very rare and associated with a greater tendency towards lupus and infections. C4 can also be low in severe liver disease, with reduced complement production.

C4 and lupus

C3 and C4 alone do not diagnose lupus. Diagnosis is based on symptoms, examination and other tests, primarily antinuclear antibodies. In confirmed lupus, falling C3 and C4 may indicate worsening disease and recovery may indicate treatment success, so a doctor monitors them over time.

C4 and hereditary angioedema

Hereditary angioedema is a rare disease in which insufficient or poorly functioning C1-inhibitor protein causes recurrent swelling of the skin and mucous membranes. It is not an allergy: swelling is usually not accompanied by hives and does not respond to antihistamines. In most patients, C4 is low even between attacks, making it a useful first step in investigation. Diagnosis is nevertheless confirmed by tests of C1-inhibitor quantity and function requested by a specialist. Tongue or throat swelling and breathing difficulty are emergencies. Read more about swelling in the article on angioedema.

How to arrange testing

You can have blood taken without an appointment or referral at one of our branches across Croatia (listed on the Contact page). Prices for all tests and panels are available in the service price list. C4 is usually measured alongside C3, so both can be tested from the same blood sample.

Frequently asked questions

Are C3 and C4 tumour markers?

No. C3 and C4 are part of the immune system and are not used to detect or monitor cancer. They may be mildly high in inflammation, including some malignancies, but this does not indicate a tumour. We explain the purpose of tumour markersin a separate article.

What does low C4 mean?

Most often increased complement consumption, for example in active lupus or cryoglobulinaemia, but it may also suggest hereditary angioedema. Mildly low C4 without symptoms is often inherited. A doctor interprets it alongside C3, symptoms and other tests, repeating measurement if needed.

What does high C4 mean?

High C4 most often accompanies inflammation or infection, when the liver produces more complement. It rarely has particular significance alone, and a doctor interprets it alongside inflammatory markers such as CRP.

Can C3 and C4 show whether I have weak immunity?

Generally not. With frequent or unusual infections, a doctor first assesses blood count and immunoglobulins, such as IgG, and requests complement tests specifically when symptoms suggest deficiency.