What is a Complement component 4 (C4) test?

From the Guidelines

A Complement component 4 (C4) test is a blood test used to measure the level of C4, a protein that is part of the complement system, to help diagnose and monitor certain conditions, such as hereditary angioedema (HAE) and acquired C1 inhibitor deficiency.

Uses of C4 Test

• The C4 test is used as a screening tool to exclude a diagnosis of HAE, with low C4 levels indicating a possible diagnosis of HAE 1
• It is also used to monitor the effectiveness of treatment for HAE and other conditions that affect the complement system
• The test can help differentiate between HAE and other forms of angioedema, such as acquired C1 inhibitor deficiency and angiotensin-converting enzyme (ACE) inhibitor-associated angioedema 1

Interpretation of Results

• A low C4 level can indicate a diagnosis of HAE or acquired C1 inhibitor deficiency, while a normal C4 level can help rule out these conditions 1
• The results of the C4 test should be interpreted in conjunction with other laboratory tests, such as C1INH antigen and functional levels, to confirm a diagnosis of HAE or other conditions

Clinical Significance

• The C4 test is an important tool in the diagnosis and management of HAE and other conditions that affect the complement system
• It can help healthcare providers make informed decisions about treatment and monitoring, and can help improve patient outcomes 1

Key Points

• The C4 test measures the level of C4, a protein that is part of the complement system
• It is used as a screening tool to exclude a diagnosis of HAE and to monitor the effectiveness of treatment
• The results of the C4 test should be interpreted in conjunction with other laboratory tests to confirm a diagnosis of HAE or other conditions
• The C4 test is an important tool in the diagnosis and management of HAE and other conditions that affect the complement system 1

From the Research

Complement Component 4 (C4) Test

• The Complement component 4 (C4) test is used to measure the level of C4 protein in the blood, which is an important part of the immune system's complement pathway 2, 3.
• C4 plays a crucial role in the body's defense against infections and inflammatory processes, and abnormalities in C4 levels have been linked to various diseases, including autoimmune disorders and infections 3, 4.
• The C4 test can be used to diagnose and monitor conditions such as lupus, rheumatoid arthritis, and certain types of kidney disease 2, 5.
• The test can also be used to predict the risk of stroke in patients with known or suspected coronary artery disease, as low levels of C4 have been associated with an increased risk of stroke 5.

Clinical Importance

• Quantification of C4A and C4B genes has great clinical importance, as unbalanced production of these proteins may be associated with pathological immune processes 2.
• The C4 test can help identify individuals with C4 deficiency, which can increase the risk of infections and autoimmune disorders 3.
• The test can also be used to monitor the effectiveness of treatments for conditions related to C4 abnormalities 4.

Methods of Measurement

• C4 levels can be measured using various methods, including capillary gel electrophoresis, allele-specific PCR, and CGE separation 2.
• Purification of human C4 and sample preparation for structural biology applications can be challenging due to low yields and complexity of recombinant C4 production protocols 6.
• Crystal and solution structures of C4b have been determined, providing molecular details of the rearrangement accompanying C4 cleavage and suggesting intramolecular flexibility of C4b 4.