Complement C3
C3· also: Complement C3, C3 complement
Clinical Overview
C3 (Complement component 3) is the most abundant protein in the complement system — the arm of innate immunity responsible for clearing pathogens and immune complexes. C3 acts as a central hub connecting both classical and alternative complement pathways. Low C3 indicates complement consumption (being used up) by immune complex disease, while high C3 is a non-specific acute phase response.
Why This Test Matters
Low C3 combined with low C4 is the classic laboratory pattern of active Systemic Lupus Erythematosus (SLE), particularly lupus nephritis. In lupus, immune complexes (containing anti-dsDNA) deposit in tissues and activate complement, consuming both C3 and C4. Serial C3 monitoring, alongside anti-dsDNA and urinalysis, guides treatment intensity. In contrast, low C3 with normal C4 suggests activation via the alternative pathway (e.g., C3 nephritic factor in membranoproliferative glomerulonephritis, or hereditary C3 deficiency). C3 is also an acute phase reactant — it can rise in infection and inflammation, masking underlying consumption.
Reference RangesWHO/IFCC standards
| Age Group | Reference Range | Unit | Notes |
|---|---|---|---|
| Adults (18–64) | 90 – 180 | mg/dL | — |
Also reported in: g/L.
What Causes Abnormal Results?
High C3 Causes
- Acute phase reaction (infection, trauma, malignancy — C3 is an acute phase protein)
- Obesity
- Pregnancy
Low C3 Causes
- Active SLE / lupus nephritis (immune complex consumption — most common clinical cause)
- Membranoproliferative glomerulonephritis (MPGN) with C3 nephritic factor
- Post-streptococcal glomerulonephritis (transient, normalizes within weeks)
- Hereditary C3 deficiency (rare — presents with severe recurrent bacterial infections)
- Cryoglobulinemia
- Infective endocarditis (subacute)
Signs & Symptoms to Watch For
How to Prepare for This Test
No fasting required. C3 should be measured alongside C4 and anti-dsDNA for complete lupus activity assessment. Process sample promptly — complement proteins can degrade if sample is left at room temperature.
Factors That Can Affect Results
- Sample handling (C3 degrades if sample sits at room temperature — process promptly or keep on ice)
- Acute phase reaction can mask low C3 (infection or inflammation raises C3, hiding lupus-related consumption)
- Rare C3 null alleles can cause constitutional low C3 without disease
Related Topics
Frequently Asked Questions
Why are C3 and C4 low in lupus flares?
In active lupus, anti-dsDNA antibodies form immune complexes with DNA released from damaged cells. These complexes activate complement through the classical pathway, which consumes both C4 (early in the pathway) and C3 (the central component). Low C3 and C4 together with high anti-dsDNA and proteinuria is the classic pattern of lupus nephritis. When treatment (usually corticosteroids and immunosuppressants) suppresses inflammation, complement levels return to normal as consumption decreases.
What if only C3 is low but C4 is normal?
Low C3 with normal C4 suggests alternative pathway activation rather than classical pathway activation. This pattern is seen in C3 nephritic factor-related MPGN (a rare kidney disease), hereditary factor H deficiency (which impairs alternative pathway regulation), or dense deposit disease. This pattern is not typical of lupus and warrants referral to nephrology for further evaluation including kidney biopsy.