Complement
At a Glance
Why Get Tested?
To determine whether deficiencies or abnormalities in complement system proteins are contributing to increased infections or autoimmune disease. To monitor the activity of certain autoimmune diseases. To help diagnose hereditary angioedema
When to Get Tested?
When you have recurrent microbial (usually bacterial) infections, unexplained episodes of swelling, or symptoms related to certain autoimmune disorders. Periodically to help monitor a known long term disease such as systemic lupus, that affects the complement system.
Sample Required?
A blood sample taken from a vein in your arm
Test Preparation Needed?
None
The Test Sample
What is being tested?
Complement tests measure the quantity or activity of complement proteins in the blood. The complement system is composed of a set of circulating blood proteins that work together to promote immune and inflammatory responses. Their principal role is to destroy foreign substances like bacteria and viruses. The nine primary complement proteins are designated C1 through C9. These components are assisted and regulated by several subcomponents, inhibitors, and regulators.
The complement system is part of the body's innate immune system. The acquired immune system, defends against infectious threats by producing an antibody and cellular response which is highly specific, but slow to mature, In contrast, the innate immune system is non-specific but can respond more quickly to foreign substances. However, the innate immune system does not maintain a memory of previous encounters, and is not as powerful as the antibody response. As part of the innate immune system, the complement system has evolved to recognize antigen-antibody complexes (immune complexes) as well as certain structures and polysaccharides (complex carbohydrates) found on the outside membranes of microorganisms and other foreign cells.
Complement activation may be initiated in several different ways. These are termed classical, alternative or lectin pathways. However, the final product from all activation pathways is the same – the formation of the Membrane Attack Complex (MAC). Complement activation causes several things to happen:
- The MAC binds to the surface of each microorganism or abnormal cell that has been targeted for destruction. It creates a lesion (hole) in the membrane wall and causes lysis, which is destruction of the cell by letting the contents out – like piercing a water-filled balloon.
- It increases the permeability of blood vessels, allowing infection-fighting white blood cells (WBCs) to move out of the bloodstream and into the tissues.
- It attracts WBCs to the site of the infection.
- It stimulates phagocytosis, a process in which microorganisms are engulfed by white blood cells such as macrophages and neutrophils and killed.
- It increases the solubility of the immune complexes and helps to clear them out of the bloodstream.
Complement proteins both promote and regulate these activities. Inherited or acquired deficiencies or abnormalities in one or more of the complement components may thus adversely affect the integrity and function of the immune system. Deficiencies may arise because of decreased production or increased consumption of one or more complement proteins.
These tests measure the quantity or the function (activity) of complement proteins in the blood. Complement components may be measured individually and together to determine whether the system is functioning normally. C3 and C4 are the most frequently measured complement proteins. Total complement activity (CH50 or CH100, and AP50 or AP100) can be measured if a doctor suspects a deficiency that is not measured by C3 or C4. CH50/CH100 measures the function of the complete classical complement pathway, and AP50/100 measures the function of the complete alternative complement pathway.. If this measurement is significantly reduced, then each of the nine different complement levels can be measured individually to look for hereditary or acquired deficiencies.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed for complement C3 and C4 measurements. For testing complement activity, the sample must be processed and frozen within 2 hours of the blood being taken from the patient.
The Test
How is it used?
Complement tests, most commonly C3 and C4, are used to determine whether deficiencies or abnormalities in the complement system are causing, or contributing to, a patient's disease or condition. Total complement activity (CH50/CH100 and AP50/100) may be requested to look at the integrity of the entire classical complement pathway. Other complement components are used as needed to look for deficiencies. C1-inhibitor is tested in patients with recurrent swellings.
Complement testing may be used to help diagnose the cause of recurrent microbial infections, unexplained swellings (agioedema), or inflammation. It may be used to help diagnose and monitor the activity of chronic autoimmune diseases such as systemic lupus erythematosus (SLE). It may be tested and monitored in other immune complex-related diseases and conditions such as serum sickness, and some cases of rheumatoid arthritis, glomerulonephritis (a kidney disorder), and vasculitis. When immune complexes form in these diseases, complement helps to clear them from the blood, temporarily decreasing complement levels – thus the levels act as a marker of disease activity. The more active the disease, the lower the complement C3 and C4 levels.
When is it requested?
Complement testing may be requested when a person has unexplained infections, swellings, inflammation or symptoms of an autoimmune disorder such as SLE. It may also be used when a doctor suspects that someone may have an immune complex-related condition and he wants to check the the status of the complement system.
C3 and C4 levels are the most frequently requested. C3 and C4 are usually used together as the relative levels are often important. Total complement activity is usually requested in patients with recurrent infections.
Individual complement components may be requested when the total complement activity (CH50/CH100 and AP50/AP100) is abnormal to help determine which of the components are deficient or abnormal.
When a chronic immune-complex condition such as SLE has been diagnosed, complement testing may be used to help give a rough idea of the severity of the condition with the assumption that the severity is linked to the decrease in complement levels.
In patients with unexplained swellings, complement C3 and C4 are requested. If the C4 is low, then complement C1 inhibitor (a control protein of the complement pathway) is tested. C1 inhibitor deficiency also known as Hereditary Angioedema (HAE), is a condition where patients develop recurrent swellings. The level of C1 inhibitor is either low (type 1 HAE), or in type 2 HAE the C1 inhibitor is dysfunctional but the level is normal or high.
What does the test result mean?
Complement levels may be decreased due to a hereditary deficiency (relatively rare) or due to increased consumption. Hereditary deficiency in one of the complement proteins will usually lead to a high frequency of recurrent microbial infections. Decreased complement levels also are associated with an increased risk of developing an autoimmune disease. Both C3 and C4 levels are typically depressed in SLE due to consumption (only rarely due to genetic deficiency of C1q, C2, or C4).
If the deficiency is due to an underlying long-term condition, complement levels will usually return to normal if the underlying condition can be resolved.
Decreased complement levels may be seen with:
- Recurrent microbial infections (usually bacterial) – reduced secondary to consumption in severe infection (septicaemia), or genetic deficiency predisposing to infection
- Autoimmune diseases, including SLE and vasculitis due to consumption (but only rarely due to genetic deficiency of C1q, C2, or C4)
- Hereditary agioedema (hereditary C1-inhibitor deficiency)
- Acquired angioedema (acquired C1-inihibitor deficiency)
- Various types of kidney disease, including lupus nephritis, some cases of membranous nephropathy, IgA nephropathy
- Serum sickness (immune complex disease)
- Severe liver disease – impaired production in the liver
Complement protein levels are usually increased, along with other unrelated proteins called acute phase reactants, during acute or chronic inflammation. These all usually return to normal when the underlying condition is resolved. However, complement proteins are rarely measured in these conditions, compared to the widely requested C-reactive protein (CRP), and the relevance of their measurement in these situations is not reviewed here.
Is there anything else I should know?
Increased and decreased complement levels will not tell the doctor what is wrong with a person, but they can give an indication that the immune system is involved with a condition
Common Questions
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Article Sources
NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
