Unit Converter
C4 Complement factor
(Complement Component 4 – Classical Pathway Activation Marker)
Synonyms
- C4
- Complement component 4
- Complement factor 4
- Fourth complement component
- C4 protein
Units of Measurement
- µmol/L
- g/L
- mg/dL
- mg/100 mL
- mg%
- mg/mL
Description
C4 complement factor is a large plasma glycoprotein synthesized mainly in the liver.
It plays a central role in the classical and lectin complement pathways.
Activation of C4 produces:
- C4a → anaphylatoxin (pro-inflammatory)
- C4b → binds to microbial surfaces and activates C2 → eventually forms C3 convertase
C4 levels are extremely useful in diagnosing:
- SLE (Systemic Lupus Erythematosus)
- Immune complex diseases
- Classical pathway complement activation
- Hereditary angioedema (HAE) screening
Physiological Role
C4 participates in:
- Opsonization
- Clearance of immune complexes
- Activation of classical complement pathway
- Defense against encapsulated bacteria
C4 is less abundant than C3 but more specific for classical pathway diseases.
Clinical Significance
Low C4 Levels (Most Important Finding)
Indicate classical complement pathway activation or genetic deficiency.
1. Systemic Lupus Erythematosus (SLE)
- Low C4 strongly suggests active immune-complex disease.
- Often decreased along with C3.
2. Lupus Nephritis
Both C3 ↓ + C4 ↓ common during flares.
3. Hereditary Angioedema (HAE)
- C4 is persistently low in HAE types I and II
- Due to C1 inhibitor deficiency or dysfunction
- C3 is usually normal
4. Immune Complex Diseases
- Cryoglobulinemia
- Immune complex vasculitis
- Rheumatoid vasculitis
5. Severe Liver Disease
Reduced synthesis → low C4.
6. Post-infection Complement Consumption
- Post-viral or post-streptococcal immune activation
High C4 Levels
Seen in:
- Acute inflammation (mild)
- Pregnancy
- Estrogen therapy
- Obesity / metabolic syndrome
- Chronic inflammatory states
C4 is an acute-phase reactant, though less than C3.
Reference Intervals
(Tietz 8E + Mayo + ARUP + Complement Immunology Guidelines)
Adults
- 0.10 – 0.40 g/L
- 10 – 40 mg/dL
Interpretation
- Low C4 + Low C3 → Classical pathway activation (e.g., SLE).
- Low C4 + Normal C3 → Hereditary angioedema (HAE).
- Normal C4 + Low C3 → Alternative pathway disease (e.g., PSGN, C3 glomerulopathy).
Unit Meanings
| Unit | Meaning |
| µmol/L | micromole per liter (rarely used for C4) |
| g/L | grams per liter |
| mg/dL | milligrams per deciliter |
| mg% | mg per 100 mL (same as mg/dL) |
| mg/100 mL | identical to mg/dL |
| mg/mL | milligrams per milliliter |
Diagnostic Uses
1. SLE and Immune Complex Diseases
- Low during active flares
- Used to monitor treatment response
- C3 + C4 pattern essential for diagnosis
2. Hereditary Angioedema (HAE)
Key screening test:
- C4 always low
- Confirm with C1 inhibitor level/function
3. Glomerulonephritis Evaluation
When immune complexes are involved:
- MPGN
- Lupus nephritis
4. Complement Deficiency Disorders
Congenital C4 deficiency → recurrent sinopulmonary infections & autoimmune disease.
5. Monitoring Inflammatory Diseases
Assesses disease activity in vasculitis and autoimmune disorders.
Analytical Notes
- Serum sample preferred
- Complement proteins are temperature-sensitive; keep sample cold
- Freeze if delayed testing
- Measured via nephelometry or turbidimetry
- Avoid hemolysis (activates complement)
Clinical Pearls
- In HAE, C4 is always low, even between attacks.
- In SLE, falling C4 often predicts a flare.
- C4 is less abundant than C3, making it more specific for classical pathway diseases.
- Distinguish patterns:
- C3↓ + C4↓ → SLE / immune complex disease
- C4↓ + C3 normal → HAE
- C4 normal + C3↓ → alternative pathway disease
- C3↓ + C4↓ → SLE / immune complex disease
Interesting Fact
C4 gene copy number varies between individuals. People with fewer copies naturally have lower serum C4 and a higher risk of autoimmune diseases like lupus.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Complement System.
- Mayo Clinic Laboratories - C4 Complement.
- ARUP Consult - Complement Disorders.
- IFCC Immunology Committee - Complement Testing Standards.
- ACR Lupus Nephritis Guidelines.
- MedlinePlus / NIH - Complement Proteins.