Complement

At a Glance

Why Get Tested?

To determine whether complement system proteins are contributing to increased infection frequency or autoimmune disease. To monitor the activity of certain autoimmune diseases. To help diagnose hereditary angioedema.

When To Get Tested?

When you have recurrent (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?

No test preparation is needed for complement C3 and C4 measurements. For testing complement activity, the sample must be sent to the laboratory very quickly for processing.

On average it takes 7 working days for the blood test results to come back from the hospital, depending on the exact tests requested. Some specialist test results may take longer, if samples have to be sent to a reference (specialist) laboratory. The X-ray & scan results may take longer. If you are registered to use the online services of your local practice, you may be able to access your results online. Your GP practice will be able to provide specific details.

If the doctor wants to see you about the result(s), you will be offered an appointment. If you are concerned about your test results, you will need to arrange an appointment with your doctor so that all relevant information including age, ethnicity, health history, signs and symptoms, laboratory and other procedures (radiology, endoscopy, etc.), can be considered.

Lab Tests Online-UK is an educational website designed to provide patients and carers with information on laboratory tests used in medical care. We are not a laboratory and are unable to comment on an individual's health and treatment.

Reference ranges are dependent on many factors, including patient age, sex, sample population, and test method, and numeric test results can have different meanings in different laboratories.

For these reasons, you will not find reference ranges for the majority of tests described on this web site. The lab report containing your test results should include the relevant reference range for your test(s). Please consult your doctor or the laboratory that performed the test(s) to obtain the reference range if you do not have the lab report.

For more information on reference ranges, please read Reference Ranges and What They Mean.

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 protective immunity. Their principal role is to destroy bacteria and viruses. The nine main complement proteins are labelled C1 through C9. These proteins are assisted and regulated by several subcomponents, inhibitors, and regulators.

The complement system is part of the body's innate immune system.

Complement activation may be achieved in 3 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 hole and causes the cell to rupture by letting the contents leak out – like piercing a water-filled balloon.
It increases the leakiness 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 white blood cells such as macrophages and neutrophils to kill swallow and kill bacteria.
It locks up the bacteria into cage like structures that dissolve in the bloodstream which are easily cleared.

Complement proteins both promote and regulate these activities. Inherited or acquired deficiencies or abnormalities in one or more of the complement components may 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 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 an immunology specialist 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. In some rheumatologic disease C1q levels or antibodies are measured. Patients with a history of recurrent unexplained swelling may have C4 and C1 esterase inhibitor measured.

Common Questions

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 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 (angioedema), 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 decreased 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 or she wants to check 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.

Complement activity or function is usually requested in patients with recurrent infections or specific infections such as meningitis.

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 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. Rarely complement deficiency may be the cause of SLE.

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 is also known as Hereditary Angioedema (HAE) and 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 may lead to a high frequency of recurrent bacterial infections. Decreased complement levels also are associated with an increased risk of developing an autoimmune disease. 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 bacterial infections – 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 angioedema (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
What are the other parts of the innate immune system?
It includes:

The phagocytic system (white blood cells, including macrophages, neutrophils, and monocytes) - whose function is to ingest and digest invading microorganisms

Inflammatory mediators produced by various cells, including basophils, mast cells, and eosinophils

Natural killer (NK) cells that are specialised lymphocytes that kill some tumour cells, microorganisms, and cells that have been infected by viruses

Acute phase reactants and cytokines, which are a group of soluble proteins that can cause changes in the growth of many cells, including the white blood cells that produce them