Complement C4
A complement-system protein read together with C3. A low level points to active immune-complex disease — most importantly lupus, where it falls during flares — and a persistently low C4 is a key clue to the rare condition hereditary angioedema.
What it measures
C4 is a protein of the complement system, the cascade that helps the immune system fight infection and clear immune complexes. Like C3, its clinically useful signal is usually a low level, because C4 is consumed when immune complexes activate the 'classical' complement pathway. It is measured with C3 to assess autoimmune disease activity: in systemic lupus, C4 (often with C3) falls during active disease, especially with kidney involvement, and recovers with treatment — making the pair useful for monitoring. C4 has a second, distinct role: a persistently low C4 is an important screening clue for hereditary angioedema, a rare inherited condition causing recurrent episodes of deep tissue swelling. A low C4 can also reflect certain kidney diseases or inherited complement deficiencies. Like C3, it can rise non-specifically as an acute-phase protein, which is not the clinically important direction.
What a high value can mean
- Inflammation / infection — C4 is an acute-phase protein and can rise non-specifically.
- Not usually the clinically important direction — a high C4 is rarely the point of the test.
What a low value can mean
- Active lupus (SLE) — consumed by immune complexes; falls during flares, often with a low C3.
- Hereditary angioedema — a persistently low C4 is a key screening clue for this rare cause of recurrent swelling.
- Other immune-complex diseases — certain types of glomerulonephritis, cryoglobulinaemia.
- Inherited C4 deficiency — predisposes to autoimmune disease and infection.
When to discuss with a doctor
C4 is interpreted alongside C3 and the autoimmune markers, not alone. In lupus, a falling C4 (with C3) can accompany or precede a flare, especially in the kidneys, and is used to monitor disease activity. Separately, in someone with recurrent unexplained episodes of deep swelling (of the face, limbs, gut or airway) that don't respond to allergy treatment, a persistently low C4 is an important clue that prompts testing for hereditary angioedema — a condition that is managed very differently from ordinary allergic swelling. Mediora.AI shows C4 with C3, ANA and anti-dsDNA so the pattern is read together; the interpretation belongs with rheumatology or immunology.