Complement Testing: The Significance of Complement C3 and C4 Low Results

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What is Complement?

The complement system is a cascade of protein reactions that enhances the body’s ability to fight diseases. The system is triggered when an antibody produced attaches to an antigen produced by a bacteria or virus. The complement molecules are mainly protein molecules that become attached during the destruction of an infected cell, and cause it to be destroyed. After the infected cell has burst, macrophages in the blood can engulf and destroy them. The liver is the main source of production of the complement proteins.

The Complement Pathways

In biochemistry there are two pathways that will initiate the complement molecules for them to start the complement pathway. The pathways are called the classic complement pathway and the alternative complement pathway. In both pathways, important molecules called C3 and C4 are produced at key times in the system. The classic pathway is triggered mainly by the attachment of an antigen and antibody to form a complex, whereas the molecule C3b attaching to an infected cell, activates the alternative pathway.

The complement system has a specific role in the innate immune system and helping memory B cells “remember” a foreign antigen. The pathways are also used for destruction of the infected cell, and attract white blood cells to the area. The complement system can trigger swelling to deal with an infection or injury.

Why Is The Test Ordered?

The test is completed by taking a blood sample and measuring the level of free-flowing complement proteins. The complement C3 and C4 low results test is to monitor a patient’s level of complement in the disease process. The doctor can use the levels of complement to discover how mild or severe is the person’s condition. It is understood that very low level will indicate a more severe form of disease to treat.

Another reason why the levels of C3 and C4 are tested is in the case of inflammation of the body. This inflammation can result in edema. The doctor might order the C3 and C4 test to detect a disease that is difficult to treat or one that is autoimmune in its nature such as lupus.

Blood Test Results For The Complement Test

If complement C3 and C4 low results occur after testing the blood, i.e. values below 75 mg/dl, can indicate that the person has an infection that keeps recurring. It is possible to have low levels due to a deficiency disease but a complement disease is a very rare phenomenon. Certain autoimmune diseases will also have low results such as lupus. Low values for complement can also point to liver disease such as hepatitis.

Not surprisingly, kidney disease can also be a cause of low results as they help filter the blood and can remove them if the kidney is not functioning properly.

If there are C3 and C4 high results, this can confirm a diagnosis of inflammation. The pathway will produce large amounts of these complement proteins in other conditions such as cancer, as the body tries to remove the foreign cells.


Print Source: Davidson, Stanley & C. Haslett. 2002. “Davidson’s Principles and Practice of Medicine.” Churchill Livingstone, Edinburgh.

Print Source: Cotran R, Kumar V, and Robbins, SL. 1999. Robbins Pathologic Basis of Disease, 6th Ed. W.B. Saunders Company, Philadelphia.

Web Source: Lab Tests Online, American Association For Clinical Chemistry. “Complement Levels.” 2010. Available: