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C3 complement factor
(Complement Component 3 – Central Protein of the Complement Cascade)
Synonyms
- C3
- Complement component 3
- Complement 3
- C3 protein
- Third complement factor
Units of Measurement
- g/L
- mg/dL
- mg/100 mL
- mg%
- mg/mL
Description
Complement C3 is the central and most abundant protein of the complement system, a major part of innate immunity.
C3 is produced mainly by the liver and participates in:
- Classical pathway
- Alternative pathway
- Lectin pathway
Activation of C3 → formation of C3a and C3b:
- C3a → anaphylatoxin (inflammation)
- C3b → opsonization, phagocytosis, and activation of C5
C3 level reflects:
- Immune activation
- Autoimmune diseases
- Complement consumption
- Genetic complement deficiencies
Clinical Significance
Low C3 Levels (Most Important)
Low C3 indicates complement consumption or genetic deficiency.
1. Immune Complex Diseases
- Systemic lupus erythematosus (SLE)
- Lupus nephritis (C3 ↓, C4 ↓)
- Immune complex vasculitis
2. Complement Activation (Alternative Pathway)
- Post-streptococcal glomerulonephritis (PSGN)
- C3 ↓ with normal C4
- C3 ↓ with normal C4
- Membranoproliferative GN
- C3 glomerulopathy
- Atypical HUS
3. Sepsis / Severe Infection
Massive complement activation → low C3.
4. Liver Disease
Reduced synthesis of C3.
5. Genetic C3 Deficiency
- Recurrent bacterial infections
- Neisseria infections
High C3 Levels
Indicative of acute-phase response or metabolic disease.
Seen in:
- Obesity
- Metabolic syndrome
- Diabetes
- Pregnancy
- Acute inflammation
- Some malignancies
C3 is an acute-phase protein, so mild elevation is common.
Reference Intervals
(Tietz 8E + Mayo + ARUP + Complement Guidelines)
Adults
- 0.90 – 1.80 g/L
- 90 – 180 mg/dL
Children
- Slightly lower in early infancy
- Reaches adult level by 1 year of age
Interpretive Patterns
- Low C3 + Low C4 → classical pathway activation (SLE)
- Low C3 + Normal C4 → alternative pathway activation (PSGN, C3G)
Unit Meanings
| Unit | Meaning |
| 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. Autoimmune Diseases
- Especially SLE and lupus nephritis
- Monitored during flare and remission
- Falling C3 → increasing disease activity
2. Glomerulonephritis
- PSGN: low C3, normal C4
- MPGN and C3 glomerulopathy: persistent low C3
3. Severe Infections & Sepsis
Excessive complement activation decreases C3.
4. Congenital Complement Deficiencies
Low C3 predisposes to recurrent pyogenic infections.
5. Acute Inflammation & Metabolic Syndrome
C3 rises as an acute-phase reactant.
Analytical Notes
- Serum preferred
- Avoid hemolysis (complement activation)
- Frozen samples stable
- Nephelometry and turbidimetry are standard measurement methods
- C3 alone cannot diagnose disease; must be interpreted with:
- C4
- CH50 (total complement activity)
- Clinical findings
- C4
Clinical Pearls
- Low C3 with normal C4 strongly suggests PSGN or alternative pathway disease.
- Low C3 + Low C4 suggests SLE or classical pathway activation.
- C3 is both a complement factor and an acute-phase reactant.
- Persistently low C3 in children → evaluate for C3 glomerulopathy.
- High C3 correlates with insulin resistance and cardiovascular risk.
Interesting Fact
C3 is one of the most evolutionarily conserved immune proteins - it exists even in primitive organisms that have no antibodies, underscoring its central role in innate immunity.
References
- Tietz Clinical Chemistry & Molecular Diagnostics, 8th Edition - Complement System.
- Mayo Clinic Laboratories - Complement C3.
- ARUP Consult - Complement Testing.
- IFCC Immunology Standards - Complement Activation.
- ACR Lupus Nephritis Guidelines.
- MedlinePlus / NIH - Complement System Overview.