Overview
The Complement C4 Blood Test measures the level of complement component 4 (C4) in the blood. C4 is a vital protein of the immune system, specifically part of the complement system, which helps fight infections, remove damaged cells, and regulate inflammation.
This test is commonly used to evaluate immune system activity, diagnose autoimmune disorders like Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), and to monitor complement system disorders or inflammatory diseases.
Abnormal C4 levels — whether low or high — can indicate immune dysfunction, complement consumption, chronic infection, or active inflammation in the body.
What is the Complement C4 Blood Test?
The Complement C4 test is a simple blood test that measures how much C4 protein is present in your bloodstream. This protein works with other complement proteins (like C3) to form a powerful defense mechanism that destroys bacteria, viruses, and other foreign substances.
C4 plays a crucial role in the classical and lectin complement pathways — two key immune response systems that become active when the body detects harmful microbes or immune complexes (antigen–antibody clusters).
Doctors often order this test to:
- Detect autoimmune diseases (e.g., lupus, rheumatoid arthritis).
- Evaluate chronic inflammation or infection.
- Monitor complement deficiencies or kidney diseases.
- Check disease activity in patients already diagnosed with autoimmune conditions.
Where It Is Produced in the Body
The C4 protein is mainly synthesized in the liver by specialized cells called hepatocytes.
Smaller amounts are also produced in immune cells, including monocytes and macrophages, especially during infections or inflammatory responses.
After synthesis, C4 circulates in the blood plasma as an inactive protein. When the immune system detects an infection or antigen–antibody complex, enzymes activate C4, triggering a cascade of reactions that enhance immune defense and inflammation.
Main Functions and Importance
Complement C4 has several important roles in maintaining the body’s immune balance and protecting against infections:
- Supports classical and lectin complement pathways
→ Helps the immune system recognize and destroy harmful microbes. - Clears immune complexes
→ Removes antigen–antibody complexes that could otherwise cause tissue damage. - Enhances phagocytosis and cell lysis
→ Helps immune cells “eat” and destroy bacteria or damaged cells. - Regulates inflammation
→ Balances inflammatory responses to prevent excessive tissue damage. - Aids in diagnosis of immune and inflammatory diseases
→ Acts as a clinical marker for autoimmune and complement system activity.
Because of these functions, the C4 level is often measured along with C3 to provide a complete picture of immune system function.
Causes of Low C4 Levels
Low levels of C4 can occur when the body is either consuming too much of the protein (due to overactivation of the immune system) or producing too little.
Common causes include:
- Autoimmune diseases such as Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis, where complement proteins are consumed during inflammation.
- Hereditary angioedema (HAE) — a rare inherited condition caused by complement deficiency.
- Severe liver disease — reduces complement synthesis since the liver produces most complement proteins.
- Chronic infections — continuous immune activation can deplete complement levels.
- Glomerulonephritis — inflammation of kidney filters leading to complement usage.
Symptoms of Low C4 Levels
Low C4 itself doesn’t cause symptoms, but the underlying condition often does. Common signs include:
- Frequent or recurrent infections, especially bacterial.
- Swelling or angioedema, common in hereditary C4 deficiency.
- Fatigue, joint pain, or skin rash, seen in lupus and other autoimmune diseases.
- Kidney problems, such as protein in the urine, swelling of legs, or puffiness around the eyes.
- Slow healing or chronic inflammation.
If a low C4 level is found, doctors may order related tests like C3, CH50, or ANA (Antinuclear Antibody Test) to identify the root cause.
Causes of High C4 Levels
High levels of C4 are generally linked to increased production during inflammation, infection, or certain diseases.
Common causes include:
- Acute or chronic inflammation — from infections or autoimmune flares.
- Tissue injury or trauma — where the immune system becomes activated.
- Certain cancers such as leukemia or lymphoma, which may increase complement activity.
- Pregnancy or physical stress, where mild elevation is normal due to hormonal and immune changes.
Symptoms of High C4 Levels
Like low levels, high C4 doesn’t cause direct symptoms. Instead, symptoms usually reflect the underlying cause:
- Fever and fatigue (infection or inflammation).
- Joint pain or swelling (autoimmune activity).
- No direct symptoms in mild or temporary increases, such as during pregnancy or recovery from infection.
High C4 levels often indicate that the immune system is active or overactive, but alone it cannot confirm a disease — it must be interpreted along with C3 and other test results.
Reference Range
The normal reference range for C4 may vary slightly by laboratory, but typically it is:
- Normal C4 Level: 10–40 mg/dL
Doctors often measure C3 and C4 together, since both proteins belong to the same complement system and abnormalities in one may affect the other.
Sample Type and Test Procedure
- Sample Type: Blood (serum)
- Sample Collection: A healthcare professional draws a small blood sample from a vein, usually from the arm.
- Test Method: The serum is analyzed in a laboratory using specialized techniques to determine the concentration of C4 protein.
No fasting or special preparation is usually required before this test.
Test Preparation
- Medications: Inform your doctor about any medications, especially steroids, immunosuppressants, or hormone therapy, as they can affect complement levels.
- Fasting: Usually not needed.
- Timing: Often tested together with C3 or other immune markers for a complete complement profile.
When to Consult a Doctor
You should talk to a healthcare provider if:
- You experience recurrent infections or unexplained fatigue and swelling.
- You have symptoms of lupus or rheumatoid arthritis such as joint pain, rashes, or fever.
- Your test shows low or high C4 levels and you need further evaluation.
- You are being monitored for autoimmune or kidney diseases and want to track your immune activity.
Doctors may recommend additional tests such as Complement C3, CH50, ANA, or Kidney Function Tests to confirm the diagnosis.
Important Word Explanations
- Complement System: A group of proteins that work with antibodies to destroy harmful microbes.
- C4 Protein: An immune system protein that helps trigger inflammation and fight infections.
- Autoimmune Disease: A disorder where the body’s immune system attacks its own tissues.
- Angioedema: Swelling under the skin, often due to allergic or hereditary causes.
- Phagocytosis: The process by which immune cells “eat” bacteria or debris.
- Glomerulonephritis: Inflammation of kidney filters, affecting their function.
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