A blood sample drawn from a vein in your arm
The complement system is complex and composed of a set of more than 30 circulating blood proteins that work together to promote immune and inflammatory responses. Its principal role is to destroy foreign pathogens like bacteria and viruses. The complement system can also be activated when the body makes antibodies against its own tissues that it thinks are foreign (autoantibodies) as happens in autoimmune diseases. Complement tests measure the quantity or activity of complement proteins in the blood.
The complement system is part of the body's innate immune system. Unlike the acquired immune system, which produces antibodies that target and protect against specific threats, the innate immune system is non-specific and can quickly respond to foreign substances. It does not require previous exposure to an invading microorganism or substance and does not maintain a memory of previous encounters.
There are nine primary complement proteins that are designated C1 through C9. These components, in addition to the remaining proteins, work together in a cascade manner by activating, amplifying, breaking apart, and forming complexes that respond to infections, non-self tissues (transplants), dead cells (apoptosis), or inflammation.
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 ("complement cascade"):
- 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 macrophages and neutrophils and killed.
- It increases the solubility of the immune complexes and helps to clear them out of the blood.
Complement tests measure the quantity or the function (activity) of complement proteins in the blood. Complement components may be measured individually or 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) can be measured if a health practitioner suspects a deficiency that is not measured by C3 or C4. CH50 measures the function of the complete classical complement pathway, C1 – C9. If this measurement is outside the normal range, 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.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
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 person's disease or condition. Total complement activity (CH50 or CH100) may be ordered to look at the integrity of the entire classical complement pathway. Other complement components are ordered as needed to look for deficiencies.
Complement testing may be used to:
- Help diagnose the cause of recurrent microbial infections (such as Streptococcus pneumoniae, Neisseria meningitides, Neisseria gonorrhea), angioedema, or inflammation.
- Help diagnose and monitor the activity and treatment of acute or chronic autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis.
- Monitor immune complex-related diseases and conditions such as glomerulonephritis (a kidney disorder), serum sickness, and vasculitis.
When is it ordered?
Complement testing may be ordered when a person has unexplained inflammation or edema or symptoms of an autoimmune disorder such as SLE. It may also be ordered when a health practitioner suspects that someone may have an immune complex-related condition and wants to check the status of the person's complement system.
Individual complement components may be ordered when the total complement activity (CH50, sometimes called CH100) is abnormal to help determine which of the components are deficient or abnormal. C3 and C4 levels are the most frequently ordered, but others, such as C1 inhibitor, may be ordered when other deficiencies are suspected. C3 and C4 are often ordered together as the relative levels are often important.
When an acute or chronic condition 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. Complement testing may also be ordered occasionally when a health practitioner wants to monitor the current activity of a condition.
What does the test result mean?
Complement levels may be decreased due to increased consumption or, more rarely, a hereditary deficiency. 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 while C3 alone is low in septicemia and infections caused by fungi or parasites such as malaria.
Decreased complement activity may be seen with:
- Recurrent microbial infections (usually bacterial)
- Autoimmune diseases, including SLE and rheumatoid arthritis
- Hereditary angioedema
- Acquired angioedema
- Various types of kidney disease, including glomerulonephritis, lupus nephritis, membranous nephritis, and IgA nephropathy as well as kidney transplant rejection
- Septicemia, shock
- Serum sickness (immune complex disease)
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 ordered C-reactive protein (CRP), and the relevance of their measurement in these situations is not reviewed here.
Increased complement activity may also be seen with:
Is there anything else I should know?
What are the other parts of the innate immune system?
- The phagocytic system (white blood cells, including neutrophils and monocytes/macrophages), whose function is to ingest and digest invading microorganisms
- Inflammatory mediators produced by various cells, including basophils, mast cells, and eosinophils
- Natural killer (NK), B and T cells that are specialized lymphocytes that kill some tumors 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
On This Site
Elsewhere On This Web
National Institute of Allergy and Infectious Diseases: The Immune System
KidsHealth.org: Immune System
National Cancer Institute: Understanding Cancer Series, The Immune System
Genetics Home Reference: Hereditary angioedema