Complement 3 (C3)

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Suspected autoimmune disease, Monitor glomerulonephritis or nephrotic syndrome

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Complement 3 (C3) Test Information Guide

Why is it done?
- Measures the level of complement protein C3 in the blood, which is a critical component of the immune system's complement cascade responsible for fighting infections and inflammatory responses
- Evaluates immune system function and helps diagnose autoimmune and infectious diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and post-streptococcal glomerulonephritis
- Monitors disease activity and response to treatment in patients with known complement-mediated disorders
- Assists in investigating recurrent infections, persistent inflammation, or unexplained symptoms suggesting immune dysfunction
- Typically ordered when patients present with symptoms of autoimmune disease, persistent infections, or when other serologic tests suggest complement activation
Normal Range
- Reference Range: 79-152 mg/dL (may vary slightly between laboratories; approximately 0.79-1.52 g/L)
- Units of Measurement: mg/dL (milligrams per deciliter) or g/L (grams per liter)
- Normal Result: C3 levels within the reference range indicate normal complement system function and adequate immune response capability
- Low C3 (Hypocomplementemia): Below 79 mg/dL suggests increased complement consumption or activation, often indicating active disease or immune-mediated processes
- High C3 (Hypercomplementemia): Above 152 mg/dL is less common but may indicate acute phase response to infection or inflammation
Interpretation
- Low C3 Levels (<79 mg/dL): Indicates active complement activation and consumption; commonly seen in SLE flares, active glomerulonephritis, membranoproliferative glomerulonephritis, post-infectious glomerulonephritis, bacterial endocarditis, or active vasculitis. May also indicate complement deficiency states.
- Normal C3 with Low C4: Suggests classical pathway activation; commonly associated with SLE, serum sickness, or immune complex disease
- Low C3 with Normal C4: Suggests alternative pathway activation; associated with membranoproliferative glomerulonephritis type II/III, post-streptococcal glomerulonephritis, or C3 glomerulonephritis
- Persistently Low C3: May indicate C3 nephritic factor or genetic C3 deficiency; warrants further investigation and specialist evaluation
- Serial C3 Measurements: Rising levels may indicate disease remission or treatment response, while persistently low or falling levels suggest continued disease activity
- Factors Affecting Results: Active infection, inflammation, recent vaccination, corticosteroid therapy, pregnancy, estrogen use, malnutrition, liver disease, and sample handling can all influence C3 levels
Associated Organs
- Primary Systems: Immune system (complement cascade), kidneys, blood vessels, and bone marrow. C3 is produced primarily by the liver and to a lesser extent by other tissues.
- Associated Kidney Diseases: Post-streptococcal glomerulonephritis, lupus nephritis, membranoproliferative glomerulonephritis, C3 glomerulonephritis, IgA nephropathy, and membranous nephropathy
- Associated Autoimmune Conditions: Systemic lupus erythematosus, rheumatoid arthritis, antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and polyarteritis nodosa
- Associated Infections: Bacterial endocarditis, meningococcemia, severe bacterial infections, sepsis, and chronic infections
- Other Conditions: Cryoglobulinemia, hereditary angioedema, complement deficiencies, liver cirrhosis, and malnutrition
- Potential Complications: Severe or persistent low C3 may lead to kidney damage, progressive renal failure, increased susceptibility to infections (especially encapsulated bacteria), and thrombotic microangiopathy
Follow-up Tests
- Complement Component C4: Measures classical pathway component; helps differentiate between complement pathway activation patterns
- Total Complement Activity (CH50): Evaluates overall complement system function and classical pathway integrity
- ANA (Antinuclear Antibody) and Anti-dsDNA: Assess for systemic lupus erythematosus and other autoimmune diseases
- ESR and CRP: Markers of inflammation that complement C3 assessment in evaluating disease activity
- Renal Function Tests (BUN, Creatinine, Urinalysis): Essential for detecting kidney involvement in complement-mediated diseases
- Kidney Biopsy with Immunofluorescence: Definitive diagnosis for glomerulonephritis and assessment of C3 deposition patterns
- C3 Nephritic Factor Testing: Specialized test for persistent C3 glomerulonephritis; evaluates alternative pathway dysregulation
- ANCA Panel: When vasculitis is suspected as cause of low C3
- Imaging Studies: Ultrasound or MRI of kidneys if kidney disease suspected
- Monitoring Frequency: Serial C3 levels typically measured every 4-12 weeks depending on disease activity, treatment initiation, or clinical changes; more frequent monitoring during acute flares
Fasting Required?
- Fasting Requirement: No - Fasting is NOT required for C3 complement testing
- Blood Collection: Can be performed at any time of day regardless of food intake. Blood sample drawn via venipuncture into a standard collection tube (typically gold-top serum separator tube)
- Medication Instructions: Continue all regular medications unless specifically instructed otherwise by healthcare provider. Some medications may affect C3 levels but should not be discontinued without medical consultation
- Patient Preparation: No special preparation needed; routine venipuncture precautions apply (keep arm relaxed, avoid excessive talking during draw)
- Sample Handling: Samples should be processed promptly and kept at room temperature or refrigerated per laboratory protocols. Improper handling or prolonged storage may result in falsely low values
- Timing Considerations: When possible, collect serial samples at consistent times to reduce variability from diurnal variations in complement levels

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