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Complement

Also known as: C1; C1q; C2; C3; C4; Total Complement; CH50; CH100; Total Hemolytic Complement Activity; C1 esterase inhibitor
Formal name: Complement Activity; Complement Component C3; Complement Component C4
Related tests: Antibody Tests; ESR; CRP; RF; ANA; Autoantibodies

At a Glance

Why Get Tested?

To determine whether deficiencies or abnormalities in complement system proteins are contributing to increased infections or increased autoimmune activity; to monitor the activity of autoimmune diseases; to help diagnose hereditary angioedema

When to Get Tested?

When you have recurrent microbial (usually bacterial) infections, unexplained inflammation or edema, or symptoms related to an autoimmune disorder; periodically to help monitor a known acute or chronic condition that affects the complement system

Sample Required?

A blood sample drawn 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 and inhibitors.

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 advance exposure to an invading microorganism or substances and does not maintain a memory of previous encounters. 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 macrophages and neutrophils and killed.
  • It increases the solubility of the immune complexes and helps to clear them out of the serum.

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 use 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) can be measured if a doctor 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.

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.

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 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 ordered to help diagnose the cause of recurrent microbial infections, angioedema, or inflammation. It may be used to help diagnose and monitor the activity of acute or chronic autoimmune diseases such as systemic lupus erythematosus (SLE). It may be tested and monitored with immune complex-related diseases and conditions such as glomerulonephritis (a kidney disorder), serum sickness, rheumatoid arthritis, and vasculitis. When immune complexes form, complement helps to clear them from the blood, temporarily decreasing complement levels.

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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 doctor suspects that someone may have an immune complex-related condition and he wants to check the status of the person's complement system.

C3 and C4 levels are the most frequently ordered, but others, such as C1 inhibitor, may be ordered when other deficiencies are suspected. Individual complement components may be ordered when the total complement activity (CH50 or CH100) is abnormal to help determine which of the components are deficient or abnormal. 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 doctor wants to monitor the current activity of a condition.

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What does the test result mean?

Looking for reference ranges?

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 while C3 alone is low in septicemia and infections caused by fungi or parasites.

If the deficiency is due to an underlying acute or chronic condition, complement levels will usually return to normal if the underlying condition can be resolved.

Decreased complement levels may be seen with:

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.

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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.

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Common Questions

1.  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 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.

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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.

Sources Used in Current Review

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(© 1995-2010). Unit Code 8174: Complement C3, Serum. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/8174 through http://www.mayomedicallaboratories.com. Accessed September 2010.

Delgado, J. et. al. (Updated 2010 June). Complement Deficiency. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/ComplementDeficiency.html?client_ID=LTD through http://www.arupconsult.com. Accessed September 2010.

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Delves, P. (Revised 2008 September). Complement System. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec13/ch163/ch163d.html?qt=complement&alt=sh through http://www.merck.com. Accessed September 2010.

Gupta, R. et. al. (Updated 2009 April 21). Complement-Related Disorders. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/136368-overview through http://emedicine.medscape.com. Accessed September 2010.

Pagana, K. D. & Pagana, T. J. (© 2007). Mosby's Diagnostic and Laboratory Test Reference 8th Edition: Mosby, Inc., Saint Louis, MO. Pp 288-289.

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Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

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The Complement System. The Merck Manual of Diagnosis and Therapy, Section 12, Immunology; Allergic Disorders, Chapter 146. Biology Of The Immune System [On-line information]. Available online at http://www.merck.com/pubs/mmanual/section12/chapter146/146d.htm through http://www.merck.com.

Kovacs, B. (2001 November 17). Complement. MEDLINEplus Health Information, Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003456.htm.

Kovacs, B. (2001 October 6, Updated). C4 level. MEDLINEplus Health Information, Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003354.htm.

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(1999 January 29, Updated). How Does the Immune System Work? [13 paragraphs]. National Institute of Allergy and Infectious Diseases, National Institutes of Health [On-line information]. Available online at http://www.niaid.nih.gov/publications/autoimmune/work.htm through http://www.niaid.nih.gov.

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Peng, S. (2005 April 20, Updated). Complement component 3 (C3). MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003539.htm. Accessed on 4/10/07.

Peng, S. (2005 April 20, Updated). Complement. MedlinePlus Medical Encyclopedia [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/ency/article/003456.htm. Accessed on 4/10/07.

Liszewski, M. K, et. al. (2002 June 7). Innate Immunity: The Complement System. Medscape from ACP Medicine Online [On-line information]. Available online at http://www.medscape.com/viewarticle/534974 through http://www.medscape.com. Accessed on 4/10/07.

(© 2007). Complement Disorders - Complement Activity. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Infectious_Disease/Chronic/Complement_Activity.html through http://www.arupconsult.com. Accessed on 4/10/07.

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