Complement C4
C4· also: Complement C4, C4 complement
Clinical Overview
C4 (Complement component 4) is an early-pathway complement protein involved in immune complex clearance. It is part of the classical complement pathway. Low C4 with low C3 is the hallmark of active lupus (SLE). C4 can also be low in hereditary angioedema (HAE) — a rare but life-threatening condition of recurrent swelling.
Why This Test Matters
C4 null alleles are common in the general population — approximately 35% of people carry at least one C4 null allele, which causes constitutional low C4 without any disease. This is an important source of false "low C4" results. To distinguish constitutional from consumption-related low C4, check family history, measure C3 (also low in active lupus), and measure CH50 (total complement activity). In hereditary angioedema (HAE), C4 is persistently low even between attacks — this is a useful screening finding. C1-inhibitor (C1-inh) antigen and functional levels confirm HAE diagnosis.
Reference RangesWHO/IFCC standards
| Age Group | Reference Range | Unit | Notes |
|---|---|---|---|
| Adults (18–64) | 16 – 47 | mg/dL | — |
Also reported in: g/L.
What Causes Abnormal Results?
High C4 Causes
- Acute phase response (C4 is a mild acute phase reactant)
Low C4 Causes
- Active SLE / lupus nephritis (most common clinical cause — immune complex consumption)
- Hereditary angioedema types 1 and 2 (C1-inhibitor deficiency — C4 is low even between attacks)
- C4 null alleles (genetic — no disease, just constitutional low C4)
- Infective endocarditis (subacute)
- Cryoglobulinemia (often hepatitis C-related)
- Post-infectious glomerulonephritis
Signs & Symptoms to Watch For
How to Prepare for This Test
No fasting required. Process sample promptly. C4 should be measured alongside C3 for complement panel interpretation. For HAE evaluation, also measure C1-inhibitor antigen and functional levels.
Factors That Can Affect Results
- C4 null alleles (constitutional low C4 in ~35% of population — very common source of low C4 results)
- Sample degradation if left at room temperature
- Lab variability between assay methods
Related Topics
Frequently Asked Questions
Is low C4 always a sign of lupus?
No. The most common reason for low C4 in an otherwise healthy person is a C4 null allele — a genetic variant where one or more C4 gene copies are deleted, producing less C4 protein. This is not associated with disease. True disease-related low C4 occurs in lupus (where C3 is also low and there are clinical symptoms) and hereditary angioedema (where C4 is persistently low even between attacks). An isolated low C4 without symptoms and with normal C3 is most often a C4 null allele variant.
What is hereditary angioedema and how is C4 related?
Hereditary angioedema (HAE) is caused by C1-inhibitor deficiency (types 1 and 2). C1-inhibitor normally prevents spontaneous complement activation. Without it, the classical pathway activates continuously, depleting C4. Because C4 is consumed constantly, its levels are low even between attacks — making C4 the best screening test for HAE. During an acute HAE episode (severe swelling), C4 falls even further. Throat swelling in HAE can be fatal; epinephrine does not work — specific HAE treatments (icatibant, C1-inhibitor concentrate, or ecallantide) are needed.